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MedWorm: AmphetamineSustained release methylphenidate for the treatment of ADHD in amphetamine abusers: A pilot study Abstract: The efficacy of stimulant treatment in patients with substance use disorders and comorbid attention deficit hyperactivity disorder (ADHD) has been tested for cocaine and alcohol dependence but so far no studies have been conducted in amphetamine dependent individuals.The present trial was a pilot study aiming to test the feasibility of treating amphetamine dependent patients with comorbid ADHD with central stimulant medication. The study was a double-blind, placebo controlled trial with parallel groups design comparing the efficacy of a fixed dose (72mg) of OROS methylphenidate (MPH) with placebo (PL) in reducing ADHD symptoms in currently abstinent adults with amphetamine dependence and ADHD. Twenty-four treatment seeking patients who met the DSM IV criteria for amphetamine depe... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Methylphenidate-induced impulsivity: pharmacological antagonism by {beta}-adrenoreceptor blockade This article examined the relative roles of noradrenaline and dopamine in the modulation of methylphenidate-induced impulsive responding in rats performing the 5-choice serial reaction time task. Experiment 1 examined the systemic antagonism of methylphenidate-induced impulsivity with either propranolol, a β-adrenoreceptor blocker, or prazosin, an 1-adrenoreceptor antagonist, which antagonises the locomotor activating effects of amphetamine. Propranolol completely abolished methylphenidate-induced impulsivity. This effect was centrally rather than peripherally mediated, as nadolol, a peripheral β-blocker failed to affect methylphenidate-induced premature responding. Prazosin partially attenuated the methylphenidate-mediated increase in premature responding. A second experiment ex... Brattleboro (BRAT) rats are a mutant variant of the Long-Evans (LE) strain deficient in the neurohormone vasopressin. BRAT rats show behavioural alterations relevant to schizophrenia. In particular, BRAT rats show deficits in prepulse inhibition (PPI) and alterations in various measures of cognition. The aim of this study was to replicate the reported PPI deficits in BRAT rats and its reversal by antipsychotic drugs and to investigate other behavioural and neurochemical characteristics. Acoustic startle reactivity, PPI, spontaneous and amphetamine-induced locomotor activity (LMA) and ex-vivo steady state neurochemistry were measured in male homozygous BRAT rats and LE rats. The effects of antipsychotics on PPI deficits were also determined. Relative to LE, BRAT rats showed enhanced startle... Repeated administration of psychostimulants to rodents can lead to behavioral sensitization. Previous studies, using nonspecific opioid receptor (OR) antagonists, revealed that ORs were involved in modulation of behavioral sensitization to methamphetamine (METH). However, the contribution of OR subtypes remains unclear. In the present study, using [mu]-OR knockout mice, we examined the role of [mu]-OR in the development of METH sensitization. Mice received daily intraperitoneal injection of drug or saline for 7 consecutive days to initiate sensitization. To express sensitization, animals received one injection of drug (the same as for initiation) or saline on day 11. Animal locomotor activity and stereotypy were monitored during the periods of initiation and expression of sensitization. Al... Authors: Rutsuko Ito & Melissa Canseliet Keywords: Dopamine; Addiction & Substance Abuse; Learning & Memory; Schizophrenia/Antipsychotics; Amphetamine; Sensitization; hippocampus; amygdala (Source: Neuropsychopharmacology) Mephedrone: classifying 'legal highs' | David Nutt Until we know the real harm of legal recreational drugs such as mephedrone, they should be put into a holding 'class D'A couple of weeks ago, seven students from Lancaster University were arrested for possession of a drug, even though the policeman leading the arrest team made it clear that the drug was not illegal. This was not the first time the police had exhibited such behaviour in relation to this drug, so what is leading to this apparently irrational police behaviour? The drug in question is mephedrone [not to be confused with the opioid substitute treatment methadone], a synthetic stimulant drug that is relatively new on the UK drug scene although it has been popular in Israel for a number of years.Mephedrone is one of a number of so-called "legal highs" – these are drugs that use... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. There is a technology gap for ‘in-field’ detection methods that are capable of separating complex mixtures of precursor chemicals and active ingredients of amphetamine-type stimulants (ATS). The Agilent Bioanalyzer 2100 is a commercial lab-on-a-chip (LOC) device designed to separate and analyse DNA and RNA. Modification of the routine operational procedures and buffers facilitates the analysis of compounds that the instrument was not originally designed for. The limiting factor is the method of detection, which is restricted to laser-induced fluorescence. Fluorescein isothiocyanate (FITC)-derivatized ATS were chosen for method optimization on conventional capillary electrophoresis (CE). The initial parameters altered for optimization were pH, sodium dodecyl sulfate (SDS) concentration,... Pleiotrophin (PTN), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is up-regulated in the nucleus accumbens after amphetamine administration suggesting that PTN could modulate amphetamine-induced pharmacological or neuroadaptative effects. To test this hypothesis, we have studied the effects of amphetamine administration in PTN genetically deficient (PTN [minus]/[minus]) and wild type (WT, +/+) mice. In conditioning studies, we found that amphetamine induces conditioned place preference in both PTN [minus]/[minus] and WT (+/+) mice. When these mice were re-evaluated after a 5-day period without amphetamine administration, we found that WT (+/+) mice did not exhibit amphetamine-seeking behaviour, whereas, PTN [minus]/[minus] mice still sh... Naltrexone attenuates amphetamine-induced locomotor sensitization in the rat This study showed that NTX attenuates drug- and cue-induced locomotor behavior in amphetamine-conditioned animals, supporting recent clinical findings that indicated a potential role of NTX as a treatment for amphetamine dependence. (Source: Addiction Biology) Authors: Li Z, Liang Y, Boules M, Gordillo A, Richelson E Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors: NTS1 and NTS2. The present study was done to determine the roles of NTS1 and NTS2on amino acid release in striatum with the use ofNTS1 or NTS2 knock-out ((-/-)) mice given d-amphetamine. Both NTS1(-/-) and NTS2(-/-) mice had lower extracellular concentrations of D-serine in striatum than did wild type (WT) mice. NTS2(-/-) but not NTS1(-/-) mice also had significantly lower basal concentrations of glutamate in striatum as compared to that for WT mice. Systemic administration of d-amphetamine (4 mg/kg, ip) increased glutamate release by 500% in WT mice, as compared to 300% in NTS2(-/-) mice, and 250% in... In this study, we investigated the effect of a single dose of the psychostimulant amphetamine on mGluR1/5 protein expression in the rat forebrain in vivo. We found that acute systemic injection of amphetamine at a behaviorally active dose (5mg/kg) was able to reduce mGluR5 protein levels in a confined biochemical fraction of synaptosomal plasma membranes enriched from the striatum. In contrast to the striatum, amphetamine increased mGluR5 protein levels in the medial prefrontal cortex. These changes in mGluR5 expression in both the striatum and the medial prefrontal cortex were transient and reversible. In addition, protein levels of mGluR1 in the enriched synaptosomal fraction from both the striatum and the medial prefrontal cortex remained stable in response to acute amphetamine. Similar... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusions Given that accumbal outflow of DA and 5-HT, as well as LMA and stereotyped behavior, is related to gratification of stimulant drugs, this study suggests that nandrolone, at the doses tested, has a significant effect on the pleasurable properties of cocaine. Furthermore, because neurochemical and behavioral responses were still attenuated after a fairly long recovery period, it seems that nandrolone may induce long-lasting changes in the brains of rat. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-010-1796-9Authors Sanna Kurling-Kailanto, National Institute for Health and Welfare Department of Alcohol, Drugs and Addiction P.O. Box 30 00271 Helsinki FinlandAino Kankaanpää, National Institute for Health and Welfare Depart... Conclusions Dopamine does not play a major role in THC discrimination. However, activation of the dopaminergic system positively modulates the discriminative effects of THC, possibly through D2-induced elevations in brain levels of anandamide. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-010-1789-8Authors Marcello Solinas, University of Poitiers Laboratoire de Biologie et Physiologie Cellulaires, CNRS-6187 40 Avenue du Recteur Pineau 86022 Poitiers FranceGianluigi Tanda, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health Psychobiology Section, Medications Discovery Research Branch, Department of Health and Human Services Baltimore MD USACarrie E. Wertheim, National Institute on Drug Abuse, Int... Conclusions These results extend the pharmacological differentiation between scopolamine-induced disrupted and persistent LI and indicate that the scopolamine LI model may have a unique capacity to discriminate between typical APDs, atypical APDs, and cognitive enhancers. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-010-1785-zAuthors Segev Barak, Tel-Aviv University Department of Psychology Tel-Aviv 69978 IsraelIna Weiner, Tel-Aviv University Department of Psychology Tel-Aviv 69978 Israel Journal PsychopharmacologyOnline ISSN 1432-2072Print ISSN 0033-3158 (Source: Psychopharmacology) Iptakalim: A potential antipsychotic drug with novel mechanisms? This study also suggests that neuronal and astrocytic plasma membrane and/or mitochondrial K(ATP) channels may be a novel target that deserves attention for antipsychotic drug development. Future research using other sensitive tests is needed to confirm this property of iptakalim. PMID: 20184878 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology) CART peptides: regulators of body weight, reward and other functions Nature Reviews Neuroscience 11, 218 (2010). doi:10.1038/nrn2806 Author: G. Rogge, D. Jones, G. W. Hubert, Y. Lin & M. J. Kuhar Nature Reviews Neuroscience9, 747–758 (2008)In figure 4a of the article, the doses of the bilateral CART (cocaine- and amphetamine-regulated transcript) peptide infusions were incorrectly given in milligrams. In both the figure and the legend, the doses should (Source: Nature Reviews Neuroscience) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. We previously reported increased binding of (+)[11C]DTBZ (dihydrotetrabenazine), the vesicular monoamine transporter (VMAT2) positron emission tomography (PET) radioligand, in striatum of some methamphetamine users. This finding might be explained by stimulant-induced vesicular DA depletion resulting in decreased DA (+)[11C]DTBZ competition at VMAT2. In a prospective PET study, we now find that administration of an acute oral dose of amphetamine (0.4 mg/kg) to humans does not cause increased striatal (+)[11C]DTBZ binding but a slight 5% decrease. Our data suggest that a low amphetamine dose is unlikely to cause sufficient DA depletion to detect increased (+)[11C]DTBZ binding and that a higher dose might be required. Synapse 64:417-420, 2010. © 2010 Wiley-Liss, Inc. (Source: Synapse) Authors: Ermer J, Homolka R, Martin P, Buckwalter M, Purkayastha J, Roesch B The pharmacokinetics of lisdexamfetamine dimesylate, a long-acting prodrug stimulant, and its active moiety, d-amphetamine, including dose-proportionality and variability, were assessed in 20 healthy adults. Subjects received a single dose, sequentially, of 50, 100, 150, 200, and 250 mg of lisdexamfetamine dimesylate. Plasma lisdexamfetamine dimesylate and d-amphetamine were measured before dosing and 0.25 to 96 hours postdose. Dose-proportionality and intersubject and intrasubject variability of pharmacokinetic parameters were examined. Safety assessments included adverse events. All 20 subjects received 50 and 100 mg while 18, 12, and 9 subjects received 150, 200, and 250 mg of lisdexamfetamine dimesylate, r... Updated Date: Feb 18, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) Updated Date: Feb 12, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) Updated Date: Feb 12, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. 3-Iodothyronamine (T1AM) is a metabolite of thyroid hormone. It is an agonist at trace amine-associated receptor 1 (TAAR1), a recently identified receptor involved in monoaminergic regulation and a potential novel therapeutic target. Here, T1AM was studied using rhesus monkey TAAR1 and/or human dopamine transporter (DAT) co-transfected cells, and wild-type (WT) and TAAR1 knock-out (KO) mice. The IC50 of T1AM competition for binding of the DAT-specific radio-ligand [3H]CFT was highly similar in DAT cells, WT striatal synaptosomes and KO striatal synaptosomes (0.72-0.81 [mu]M). T1AM inhibition of 10 nM [3H]dopamine uptake (IC50: WT, 1.4 ± 0.5 [mu]M; KO, 1.2 ± 0.4 [mu]M) or 50 nM [3H]serotonin uptake (IC50: WT, 4.5 ± 0.6 [mu]M; KO, 4.7 ± 1.1 [mu]M) in WT and KO synaptosomes was also highl... A Genetic epilepsy rat model displays endophenotypes of psychosis. Authors: Jones NC, Martin S, Megatia I, Hakami T, Salzberg MR, Pinault D, Morris MJ, O'Brien TJ, den Buuse MV The incidence of psychosis is increased in people with epilepsy, including idiopathic generalized epilepsies. To study the biological basis for this co-morbidity, we compared GAERS, a genetic rat model of absence epilepsy, to non-epileptic control rats (NEC). Mature, 14-week old GAERS showed enhanced amphetamine-induced locomotor hyperactivity - a feature also present in young (6-week old) GAERS prior to epilepsy onset. Prepulse inhibition and its disruption by psychotropic drugs did not differ between strains, although GAERS displayed elevated startle responses at both epileptic and pre-epileptic ages. The frontoparietal cortex of GAERS displayed a twofold increase in the powe... Conclusions Following acute PCP treatment, we found no evidence of reduced reward value without the presence of confounding motor deficits. Sub-chronic PCP withdrawal also produced no decrease in reward value. Therefore, the current results indicate that neither acute PCP treatment nor sub-chronic PCP withdrawal produce consummatory anhedonia. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-010-1779-xAuthors Emma S. Lydall, Cardiff University School of Psychology Tower Building, Park Place Cardiff CF10 3AT UKGary Gilmour, Eli Lilly & Co. Ltd., Lilly Research Centre Erl Wood Manor, Sunninghill Road Windlesham Surrey GU20 6PH UKDominic M. Dwyer, Cardiff University School of Psychology Tower Building, Park Place Cardiff CF10 3AT UK Jo... This study contributes to the growing evidence that goal-seeking behaviors are mediated by a set of neural processes distinct from those governing food reward. (PsycINFO Database Record (c) 2009 APA, all rights reserved) (Source: Behavioral Neuroscience) Human sex differences in d-amphetamine self-administration Conclusion The results of this study suggest that men are more sensitive to the reinforcing effects of a high dose of d-amphetamine than women. Future research is needed that determines prospectively the reinforcing effects of weight-adjusted doses of d-amphetamine in women and men while controlling for menstrual cycle phase. (Source: Addiction) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusion The ED provides an opportunity for early intervention for patients presenting with comorbid drug and alcohol and mental health problems. Further research is needed to assess the prevalence of drug and alcohol problems in ED patients with mental health problems and to develop effective interventions in that setting. (Source: Addiction) What is the Differential Diagnosis of Failure to Thrive? Discussion Failure to Thrive (FTT) is defined as persistent weight below the 3rd percentile for age in infants and young children. The associated terms “Failure to gain weight” (FGW) or “Lack of Normal Physiologic Growth and Development” are more precise, especially for children who are not below the 3rd percentile but are losing weight over time and/or crossing percentile lines on their growth curve. For general growth parameters see How Do I Calculate Mid-Parental Height and Other Growth Parameters? About 70-80% of FTT cases have psychosocial problems that are associated with the FTT or the primary cause of the FTT. Children of older ages may also have FTT such as those with psychosocial dwarfism or eating disorders. Children with FTT have a wide range of appearan... Analytical evaluation of a rapid on-site oral fluid drug test. Authors: Goessaert AS, Pil K, Veramme J, Verstraete A There is a need for a reliable rapid on-site oral fluid test that can be used in police controls to detect impaired drivers. We evaluated the Varian Oralab(R)6 and collected two oral fluid samples from 250 subjects, one with the Varian Oralab(R)6 and one with the StatSure Saliva*Sampler. The Oralab(R)6 can detect six drug types: amphetamines, methamphetamine, cocaine, opiates, delta9-tetrahydrocannabinol (THC), and phencyclidine (PCP). On-site results were obtained within 10 to 15 min. The sample collected with StatSure was analyzed using liquid chromatography-tandem mass spectrometry after liquid-liquid extraction and these results were used as a reference to determine prevalence, sensitivity, and specificity. Two cut-off values we... Conclusions: Studies have established that moderate drinkers report a greater degree of abuse liability-related effects than do light drinkers with several different drugs, including diazepam, amphetamine, and nitrous oxide, but we were unable to establish this with the prescription opioid, oxycodone. However, we did observe sex differences in several subjective effects of oxycodone, a finding that is consistent with the extant literature showing sex differences in pharmacodynamic effects of opioids. (Source: Drug and Alcohol Dependence) Conclusions and implications: A straightforward protocol now exists to monitor NET transport rate at the level of the single nerve terminal varicosity, providing a useful tool to understand the physiology of NET regulation, the action of NET inhibitors on mature sympathetic terminals, dynamic vesicular tracking and to identify sympathetic terminals from mixed terminal populations in living organs. (Source: British Journal of Pharmacology) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Authors: Nakamoto A, Nishida M, Saito T, Kishiyama I, Miyazaki S, Murakami K, Nagao M, Namura A A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d(5) was used as an internal standard. The linear ranges were 0.01-5.0 microg mL(-1) for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 microg mL(-1) for amphetamine (AP)... COMPARATIVE EFFECTS OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE AND 4-METHYLTHIOAMPHETAMINE ON RAT LIVER MITOCHONDRIAL FUNCTION. Toxicology. 2010 Feb 4; Authors: Custódio JB, Santos MS, Gonçalves DI, Moreno AJ, Fernandes E, Bastos ML, Carvalho F, Vicente JA, Fernandes MA Ecstasy, which is used as a recreational drug, is a common street name for 3, 4-methylenedioxymethamphetamine (MDMA). Another drug of abuse chemically related, though less common than MDMA, is the amphetamine derivative 4-methylthioamphetamine (MTA). MDMA and MTA induce different systemic and organ-specific effects, including neurotoxicity, hyperthermia, nephrotoxicity, cardiotoxicity and hepatotoxicity. Therefore, it is clear that MDMA and MTA are responsible for inducing organ toxicity. The mechanisms unde... In conclusion, the results suggest that GRPR antagonists might display antioxidant properties in the brain. Content Type Journal ArticleCategory Basic Neurosciences, Genetics and Immunology - Original ArticleDOI 10.1007/s00702-010-0373-zAuthors Samira S. Valvassori, University of Southern Santa Catarina Postgraduate Program in Health Sciences, Health Sciences Unit, Laboratory of Neurosciences and National Institute for Translational Medicine 88806-000 Criciúma SC BrazilMorgana Moretti, University of Southern Santa Catarina Postgraduate Program in Health Sciences, Health Sciences Unit, Laboratory of Neurosciences and National Institute for Translational Medicine 88806-000 Criciúma SC BrazilMarcia Kauer-Sant’Anna, Federal University of Rio Grande do Sul Bipolar Disorders Program, L... NK1 (TACR1) receptor gene 'knockout' mouse phenotype predicts genetic association with ADHD In conclusion, our proposal that NK1R–/– mice offer a mouse model of ADHD was borne out by our human studies, which suggest that DNA sequence changes in and around the TACR1 gene increase susceptibility to this disorder. (Source: Journal of Psychopharmacology) Function of dopamine transporter is compromised in DYT1 transgenic animal model in vivo J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06590.x Early onset torsion dystonia (DYT1), the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein, torsinA. We previously examined the effect of the human mutant torsinA on striatal dopaminergic function in a conventional transgenic mouse model of DYT1 dystonia (hMT1), in which human mutant torsinA is expressed under the cytomegalovirus promotor. Systemic administration of amphetamine did not increase dopamine (DA) release as efficiently in these mice as compared with wild-type transgenic and non-transgenic mice. We, now, studied the contribution of the DA transporter (DAT) to amphetamine-induced DA release in hMT1 transgenic mice using in vivo no-net flux microdialysis. Thi... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. ADHD stimulants and their effect on height in children. Authors: Goldman RD QUESTION: Many more children today are diagnosed and treated for attention deficit hyperactivity disorder. Parents frequently ask me if the stimulant medications their children receive might affect their height as adults. What should I tell them? ANSWER: Stimulant medications, including methylphenidate and amphetamine, are safe and effective in children and adolescents with attention deficit hyperactivity disorder. Research on the issue of growth suppression is lacking, mostly owing to insufficient follow-up on patients' final heights. In general, the rate of height loss seems relatively small and is likely reversible with withdrawal of treatment. Clinical presentation and academic achievements should be the key to determining which drug to prescribe, the preparatio... Fatality Rates Among Young Drug Users A Cause For Concern A paper by a University of Hertfordshire academic due to be published tomorrow (29 January 2010), reports that excess ecstasy-related death rates in young users is a cause for concern. Professor Fabrizio Schifano at the University's School of Pharmacy, is lead author for a paper entitled Overview of Amphetamine-Type Stimulant Mortality Data UK, 1997 2007, which will be published in Neuropsychobiology online tomorrow... (Source: Health News from Medical News Today) Neurturin Effects on Nigrostriatal Dopamine Release and Content: Comparison with GDNF. Authors: Cass WA, Peters LE Neurturin (NTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family; and, while GDNF has been shown to increase dopamine (DA) release in normal animals, the ability of NTN to alter DA release has not been previously reported. The purpose of the present study was to determine if NTN could alter striatal DA release, and to compare the effects of NTN to GDNF. Male Fischer-344 rats were given a single injection of vehicle or 5 mug NTN or GDNF into the right substantia nigra. Three weeks later microdialysis experiments were conducted to assess striatal DA release. Basal extracellular levels of striatal DA were not affected by either NTN or GDNF. However, both NTN and GDNF led to increases in amphetamine-evoked overflow of DA from the ipsi... Conclusion: According to most prognostic factors, the patient had a statistical chance for survival of less than 1 %, not taking into account her severe state of hypoglyaemia .We suggest that this case exemplifies the need for more studies on the use of TH in non-coronary causes of OHCA. (Source: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine) In conclusion, these data provide further evidence of the important involvement of L-type calcium channels in the behavioral effects produced by ethanol. PMID: 20122967 [PubMed - as supplied by publisher] (Source: Behavioural Brain Research) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Overview of Amphetamine-Type Stimulant Mortality Data UK, 19972007 Neuropsychobiology 2010;61:122130 (DOI:10.1159/000279302) (Source: Karger Publishers) An index of fatal toxicity for drugs of misuse To determine the lethal toxicity of five commonly-used illicit substances by relating the number of associated deaths to their availability.An index of toxicity was calculated for each of five drugs [heroin, cocaine/crack, ecstasy (MDMA), amphetamine and cannabis] as the ratio of the number of deaths associated with that substance to its availability in the period 2003-2007. Three separate proxy measures of availability were used (number of users as determined by household surveys, number of seizures by law enforcement agencies and estimates of the market size). All data are related to England and Wales only.There was a broad correlation between all three denominators of availability. Not unexpectedly, heroin and cannabis showed, respectively, the highest and lowest toxicities. The index o... Authors: Hamidovic A, Dlugos A, Palmer AA, de Wit H Individuals vary in their subjective responses to stimulant drugs, and these differences are believed to be partially genetic in origin. We evaluated associations between mood, cognitive and cardiovascular responses to d-amphetamine and four polymorphisms in the dopamine transporter (SLC6A3): rs460000, rs3756450, rs37022 and rs6869645. Healthy Caucasian male and female volunteers (N = 152) participated in a double-blind, crossover design study in which they received placebo, 10 and 20 mg of d-amphetamine. We measured self-reported rating of mood, performance on the Digit Symbol Substitution Task, blood pressure and heart rate. Individuals with the C/C genotype at rs460000 (N = 83) reported approximately twofold higher ratings of stimu... Severe psychological stress in the first trimester of pregnancy increases the risk of schizophrenia in the offspring. To begin to investigate the role of glucocorticoid receptors in this association, we determined the effects of the glucocorticoid dexamethasone (2 mg/kg), administered to pregnant rats on gestation days 6-8, on maternal behaviors and schizophrenia-relevant behaviors in the offspring. Dams receiving dexamethasone exhibited increased milk ejection bouts during nursing. Offspring of dexamethasone-treated dams (DEX) showed decreased juvenile social play and a blunted acoustic startle reflex in adolescence and adulthood, effects that were predicted by frequency of milk ejections in the dams. DEX offspring also showed increased prepulse inhibition of startle and reduced amphetami... Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons Authors: Alexander B Wiltschko, Jeffrey R Pettibone & Joshua D Berke Keywords: dopamine, striatum, single-unit recordings, amphetamine, antipsychotic, psychostimulant (Source: Neuropsychopharmacology) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating, a behavior in... (Source: Proceedings of the National Academy of Sciences) Summary: Methamphetamine (MA) abuse has reached epidemic proportions in the United States. Users of MA report dramatic increases in sexual drive that have been associated with increased engagement in risky sexual behavior leading to higher rates of sexually transmitted diseases and unplanned pregnancies. The ability of MA to enhance sexual drive in females is enigmatic since related psychostimulants like amphetamine and cocaine appear not to affect sexual drive in women, and in rodents models, amphetamine has been reported to be inhibitory to female sexual behavior. Examination of MA's effects on female sexual behavior in an animal model is lacking. Here, using a rodent model, we have demonstrated that MA enhanced female sexual behavior. MA (5mg/kg) or saline vehicle was administered once ... J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06599.x The dopamine transporter (DAT) plays a key role in regulating dopaminergic signalling in the brain by mediating rapid clearance of dopamine from the synaptic clefts. The psychostimulatory actions of cocaine and amphetamine are primarily the result of a direct interaction of these compounds with DAT leading to attenuated dopamine clearance and for amphetamine even increased dopamine release. In the last decade, intensive efforts have been directed towards understanding the molecular and cellular mechanisms governing the activity and availability of DAT in the plasma membrane of the pre-synaptic neurons. This has led to the identification of a plethora of different kinases, receptors and scaffolding proteins that interact with DAT and her... In conclusion, these data demonstrate that the mutant C100 fragment is an effector of biochemical and both cognitive and non-cognitive behaviours. These transgenic mice may be a model for the psychotic features associated with early Alzheimer's Disease. PMID: 20085783 [PubMed - as supplied by publisher] (Source: Behavioural Brain Research) Characteristics of mentally ill offenders from 100 psychiatric court reports Conclusions: The ability of the legal system to detect cases was good, while the ability of the healthcare system to predict crimes and offences was weak, as 58% of cases had had previous contact with the healthcare system previously. Substance abuse, especially amphetamine abuse, played an important role. (Source: Annals of General Psychiatry) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum. Authors: Wohlfarth A, Weinmann W, Dresen S Since the late 1990s and early 2000s, derivatives of well-known designer drugs as well as new psychoactive compounds have been sold on the illicit drug market and have led to intoxications and fatalities. The LC-MS/MS screening method presented covers 31 new designer drugs as well as cathinone, methcathinone, phencyclidine, and ketamine which were included to complete the screening spectrum. All but the last two are modified molecular structures of amphetamine, tryptamine, or piperazine. Among the amphetamine derivatives are cathinone, methcathinone, 3,4-DMA, 2,5-DMA, DOB, DOET, DOM, ethylamphetamine, MDDMA, 4-MTA, PMA, PMMA, 3,4,5-TMA, TMA-6 and members of the 2C group: 2C-B, 2C-D, 2C-H, 2C-I, 2C-P, 2C-T-2, 2C-T-4, and 2C-T-7. AMT, DPT, DiPT,... KemPharm, Inc. Announces Positive Results From Phase 1 Trial Of KP106 For ADHD KemPharm, Inc. today announced positive results from a Phase 1 clinical trial of KP106, its novel prodrug for attention-deficit hyperactivity disorder (ADHD). KP106, a new chemical entity (NCE) composed of the active pharmaceutical compound d-amphetamine and a ligand, was created using KemPharm's proprietary Ligand Activated Therapy (LAT) prodrug approach. The pharmacokinetic (PK) profile of d-amphetamine released from KP106 is modified versus the profile observed with Vyvanse®, a currently marketed amphetamine-based stimulant for ADHD... (Source: Health News from Medical News Today) KemPharm, Inc. Announces Positive Results From Phase 1 Trial Of KP106 For ADHD KemPharm, Inc. today announced positive results from a Phase 1 clinical trial of KP106, its novel prodrug for attention-deficit hyperactivity disorder (ADHD). KP106, a new chemical entity (NCE) composed of the active pharmaceutical compound d-amphetamine and a ligand, was created using KemPharm's proprietary Ligand Activated Therapy (LAT) prodrug approach... (Source: ADHD News From Medical News Today) Gene Expression Profiling Identifies Key Estradiol Targets in the Frontal Cortex of the Rat. Authors: Sárvári M, Hrabovszky E, Kalló I, Galamb O, Solymosi N, Likó I, Molnár B, Tihanyi K, Szombathelyi Z, Liposits Z Estradiol modulates a wide range of neural functions in the frontal cerebral cortex where subsets of neurons express estrogen receptor-alpha and -beta. Through these receptors, estradiol contributes to the maintenance of normal operation of the frontal cortex. During the decline of gonadal hormones, the frequency of neurological and psychiatric disorders increases. To shed light on the etiology of disorders related to declining levels of estrogens, we studied the genomic responses to estradiol. Ovariectomized rats were treated with a sc injection of estradiol. Twenty-four hours later, samples from the frontal cortices were dissected, and thei... In this report, we show that molecules possessing two substrate-like phenylalkylamine moieties linked by a progressively longer aliphatic spacer act as progressively more potent DAT inhibitors (rather than substrates). One compound bearing two dopamine (DA)-like pharmacophoric 'heads' separated by an 8-carbon linker achieved an 82-fold gain in inhibition of [3H] 2[beta]-carbomethoxy-3[beta]-(4-fluorophenyl)-tropane (CFT) binding compared with DA itself; bivalent compounds with a 6-carbon linker and heterologous combinations of DA-, amphetamine- and [beta]-phenethylamine-like heads all resulted in considerable and comparable gains in DAT affinity. A series of short-chain bivalent-like compounds with a single N-linkage was also identified, the most potent of which displayed a 74-fold gain in... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Ultrastructural and neurochemical architecture of the pituitary neural lobe of Xenopus laevis. Authors: van Wijk DC, Meijer KH, Roubos EW The melanotrope cell in the amphibian pituitary pars intermedia is a model to study fundamental aspects of neuroendocrine integration. They release alpha-melanophore-stimulating hormone (alphaMSH), under the control of a large number of neurochemical signals derived from various brain centers. In Xenopus laevis, most of these signals are produced in the hypothalamic magnocellular nucleus (Mg) and are probably released from neurohemal axon terminals in the pituitary neural lobe, to stimulate alphaMSH release, causing skin darkening. The presence in the neural lobe of at least eight stimulatory factors implicated in melanotrope cell control has led us to investigate the ultrastructural architecture of this neurohemal organ, with particular atten... Parkinsonism in patients with a history of amphetamine exposure We recently found a higher rate of prolonged amphetamine exposure in patients diagnosed with Parkinson's disease (PD) than in spouse/caregiver controls. Since distinguishing features have been described in some patients with parkinsonism due to environment exposures (e.g., manganese), we sought to compare the clinical features of patients with PD with prolonged amphetamine exposure with unexposed patients with PD. Prolonged exposure was defined as a minimum of twice a week for [ge]3 months, or weekly use [ge]1 year. We reviewed the clinical records of patients with PD who had participated in a telephone survey of drug and environmental exposures and compared the clinical features of patients with a history of prolonged amphetamine exposure to patients who had no such exposure. Records were... Transgenic mice in the study of drug addiction and the effects of psychostimulant drugs The first transgenic models used to study addiction were based upon a priori assumptions about the importance of particular genes in addiction, including the main target molecules of morphine, amphetamine, and cocaine. This consequently emphasized the importance of monoamine transporters, opioid receptors, and monoamine receptors in addiction. Although the effects of opiates were largely eliminated by [mu] opioid receptor gene knockout, the case for psychostimulants was much more complex. Research using transgenic models supported the idea of a polygenic basis for psychostimulant effects and has associated particular genes with different behavioral consequences of psychostimulants. Phenotypic analysis of transgenic mice, especially gene knockout mice, has been instrumental in identifying t... Addictions and their familiality in Iceland Here, we provide an overview of previous family studies of addiction and present a new family study based on clinical data for more than 19,000 individuals who have been treated for addiction in Iceland over the last three decades. Coupled with the extensive Icelandic genealogy information, this population-based sample provides a unique opportunity for family studies. The relative risk (RR) was determined for up to fifth-degree relatives of probands diagnosed with alcohol, cannabis, sedative, and amphetamine dependence. We observe highly significant RR values for all substances ranging from 2.27 for alcohol to 7.3 for amphetamine, for first-degree relatives, and RRs significantly above 1 for distant relations, where the effect of shared environmental factors is minimized. The magnitude of ... Regulation of the dopamine transporter Dopaminergic signaling in the brain is primarily modulated by dopamine transporters (DATs), which actively translocate extraneuronal dopamine back into dopaminergic neurons. Transporter proteins are highly dynamic, continuously trafficking between plasmalemmal and endosomal membranes. Changes in DAT membrane trafficking kinetics can rapidly regulate dopaminergic tone by altering the number of transporters present at the cell surface. Various psychostimulant DAT ligands[mdash]acting either as amphetamine-like substrates or cocaine-like nontranslocated inhibitors[mdash]affect transporter trafficking, triggering rapid insertion or removal of plasmalemmal DATs. In this review, we focus on the effects of psychostimulants of addiction (particularly d-methamphetamine and cocaine) on DAT regulatio... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. This report reviews preclinical, human laboratory, and clinical trial data supporting the agonist-like approach, including risks and benefits. Future directions for development of agonist-like medications are also discussed. (Source: Annals of the New York Academy of Sciences) The drugs of abuse, methamphetamine and MDMA, produce long-term decreases in markers of biogenic amine neurotransmission. These decreases have been traditionally linked to nerve terminals and are evident in a variety of species, including rodents, nonhuman primates, and humans. Recent studies indicate that the damage produced by these drugs may be more widespread than originally believed. Changes indicative of damage to cell bodies of biogenic and nonbiogenic amine[ndash]containing neurons in several brain areas and endothelial cells that make up the blood[ndash]brain barrier have been reported. The processes that mediate this damage involve not only oxidative stress but also include excitotoxic mechanisms, neuroinflammation, the ubiquitin proteasome system, as well as mitochondrial and ne... Authors: Cservenka A, Spangler E, Cote DM, Ryabinin AE Urocortin 1 (Ucn 1) is an endogenous corticotropin releasing factor (CRF)-related peptide. Ucn 1 is most highly expressed in the perioculomotor urocortin containing neurons (pIIIu), previously known as the non-preganglionic Edinger-Westphal nucleus (npEW). Various studies indicate that these cells are involved in stress adaptation and the regulation of ethanol (EtOH) intake. However, the developmental trajectory of these neurons remained unexamined. Expression of the cocaine-and amphetamine-regulated transcript (CART), which co-localizes with Ucn 1 in the perioculomotor area (pIII) has been examined prenatally, but not postnatally. The goal of the current study was to characterize the ontogenetic profile of Ucn 1 and CART during po... Abstract: A gas chromatography–mass spectrometric (GC–MS) method was developed and validated for the determination of five psychotropic phenylalkylamine derivatives (amphetamine, AP; methamphetamine, MA; 3,4-methylenedioxyamphetamine, MDA; 3,4-methylenedioxymethamphetamine, MDMA; norketamine, NKT) in human hair. Hair samples (10mg) were washed with distilled water and acetone, mechanically pulverized for 1.5min with a bead mill, and then incubated in 1mL of methanol under ultrasonication at 50°C for 1h. The resulting solutions were evaporated to dryness, derivatized using heptafluorobutyric anhydride (HFBA) at 50°C for 30min, and analyzed by GC–MS. The linear ranges were 0.1–20.0ng/mg for AP and MA and 0.05–20.0ng/mg for MDA, MDMA, and NKT, with the coefficients of determinatio... We describe the development and validation of a method for the quantification of drugs of abuse, using gas chromatography–mass spectrometry (GC/MS), in human placenta. Concentration ranges covered were 5–500ng/g for amphetamine, methamphetamine, MDMA, methadone, cocaine, benzoylecgonine, cocaethylene, morphine, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol, nicotine, and cotinine. Intra-assay and inter-assay imprecisions were less than 15.7% for lower quality control samples and less than 14.9% for medium and high quality control samples. Recovery range was 36.2–83.7%. Placenta samples were kept at −80°C until analysis; analytes were stable after three freeze–thaw cycles (samples stored at −20°C). This accurate and precise assay has sufficient sensitivity and specificity for ... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusion: Dividing the drug concentration in oral fluid by the OF/B regression coefficient gave an acceptable estimation of high blood drug concentrations in a population, and may therefore give valuable additional information on possible drug impairment, e.g. in roadside surveys of drugs and driving. If good data on the distribution of OF/B ratios are available, a Monte Carlo simulation may give better accuracy. (Source: Forensic Science International) Since 1997, the use of methamphetamine as a drug of abuse has been widespread in the United States. While several forms of amphetamine are useful in some areas of medicine, methamphetamine as an abused substance is associated with severe and multifaceted c... (Source: SafetyLit: All (Unduplicated)) Poster 23: Pharmacology of the Dopaminergic Stabilizer Pridopidine (ACR16) Conclusions: Pridopidine stabilizes psychomotor activity by functional D2 antagonism and strengthening of cortical glutamate functions. Strengthening of cortical glutamatergic transmission may be key to the efficacious in vivo effects of pridopidine in states of hyperdopaminergia and hypoglutamatergia. The dopaminergic stabilizer pridopidine may offer clinical relief of psychomotor symptoms arising from dopaminergic dysfunction in HD. (Source: Neurotherapeutics) Conclusions/interpretation The significant correlation between expression of a unique splicing form of TCF7L2, named here TCF7L2-NE, and CART, the gene for an anorexigenic neurohormone expressed in the central and peripheral nervous system, suggests that these transcripts may share neuroendocrine functions important for brain, gut and pancreatic islets. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00125-009-1640-0Authors L. Prokunina-Olsson, National Institutes of Health Laboratory of Translational Genomics, National Cancer Institute 8717 Grovemont Circle Bethesda 20892-4605 MD USAJ. L. Hall, University of Minnesota Lillehei Heart Institute, Department of Medicine, The Developmental Biology Center Minneapolis MN USA Journal DiabetologiaOn... Home Office announces ban of "legal highs" Source: News Distribution Service Area: News The Home Office has announced the ban of the following drugs known as 'legal highs' under the Misuse of Drugs Act 1971: - Chemical solvent Gamma-Butyrolactone (GBL) and 1,4-Butanediol (1,4-BD) - which are converted into gamma-hydroxybutyrate (GHB)- now controlled as Class C drugs when intended for human consumption - Synthetic cannabinoids - man-made chemicals sprayed on herbal smoking products such as 'Spice', which act on the body in a similar way to cannabis but can be far more potent - now controlled as Class B drugs alongside cannabis - Benzylpiperazine (BZP) and related piperazines, which are stimulants similar to amphetamine - now controlled as Class C drugs - Oripavine, an alkaloid found in poppy straw of the opium poppy w... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Striatal and extrastriatal dopamine release measured with PET and [18F] fallypride The amphetamine challenge, in which positron emission tomography (PET) or single photon emission computed tomography radioligand binding following administration of amphetamine is compared to baseline values, has been successfully used in a number of brain imaging studies as an indicator of dopaminergic function, particularly in the striatum. [18F] fallypride is the first PET radioligand that allows measurement of the effects of amphetamine on D2/D3 ligand binding in striatum and extra-striatal brain regions in a single scanning session following amphetamine. We scanned 15 healthy volunteer subjects with [18F] fallypride at baseline and following amphetamine (0.3 mg/kg) using arterial plasma input-based modeling as well as reference region methods. We found that amphetamine effect was robu... In this study, we examined whether the endogenous peroxisome proliferator-activated receptor-[alpha] (PPAR-[alpha]) agonist, oleoylethanolamide (OEA) protects against these MDMA-induced deficits. Mice were pretreated twice a day with OEA (0, 5, and 25 mg/kg) 30 min before an injection of MDMA (30 mg/kg) or saline during four consecutive days. Twenty-four hours after the last treatment, animals were trained in an active avoidance task for two consecutive weeks. After a 5-day resting period, a recall session was performed. Mice treated with MDMA showed reduced learning and recall of the task when compared with saline-treated controls. OEA at 5 mg/kg ameliorated and at 25 mg/kg worsened this deficit. Dopamine transporter (DAT)-binding sites significantly decreased 4 days after the last MDMA a... Sex-related effects of agmatine on caffeine-induced locomotor activity in Swiss Webster mice. Authors: Uzbay T, Kose A, Kayir H, Ulusoy G, Celik T In mammalian brain, agmatine is an endogenous amine that is synthesized through the decarboxylation of L-arginine by arginine decarboxylase. It has been proposed as a new neurotransmitter and/or neuromodulator. It was shown that agmatine had some beneficial effects in animal models of opioid and alcohol addiction. Locomotor stimulant properties of drugs such as ethanol, caffeine, nicotine and amphetamine have been linked to their addictive properties. The present study investigates the effects of agmatine on caffeine-induced locomotor activity both in male and female mice. Adult Swiss Webster mice were used in the study. Locomotor activity was measured for 30min immediately following caffeine (2.5, 5, 10 and 20mg/kg, i.p.) or saline ... Atomoxetine attenuates dextroamphetamine effects in humans. Conclusions: These findings are consistent with previous preclinical studies supporting the role of the noradrenergic system in mediating acute amphetamine responses. Scientific significance: Atomoxetine's capacity to attenuate some of the physiological and subjective responses to dextroamphetamine supports its potential use for stimulant addiction. PMID: 20014909 [PubMed - in process] (Source: The American Journal of Drug and Alcohol Abuse) Conclusions Thus, selectively inhibiting the DAT produced a long-lasting cross-strain behavioral profile in mice that was consistent with that observed in manic BD patients. These findings support the use of selective DAT inhibition in animal models of the impaired dopaminergic homeostasis putatively involved in the pathophysiology of BD mania. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1744-8Authors Jared W. Young, University of California, San Diego Department of Psychiatry 9500 Gilman Drive MC 0804 La Jolla CA 92093-0804 USAAndrew K. L. Goey, Utrecht University Sorbonnelaan 16 3584 CA Utrecht The NetherlandsArpi Minassian, University of California, San Diego Department of Psychiatry 9500 Gilman Drive MC 0804 La Jolla CA 92093-... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusions Our findings suggest that repeated, behaviorally contingent exposure to methylphenidate during adolescence enhances responsivity to the locomotor-stimulating and neuronal activating effects of amphetamine but not incentive motivation. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1745-7Authors Christie L. Burton, University of Toronto Department of Psychology 100 St. George Street Toronto ON Canada M5S 3G3José N. Nobrega, University of Toronto Department of Psychology 100 St. George Street Toronto ON Canada M5S 3G3Paul J. Fletcher, University of Toronto Department of Psychology 100 St. George Street Toronto ON Canada M5S 3G3 Journal PsychopharmacologyOnline ISSN 1432-2072Print ISSN 0033-3158 (Source: Psychopharmac... Short-term outcomes of mothers and infants exposed to antenatal amphetamines Conclusions: Amphetamine-exposed mothers and infants in public hospitals of NSW and the ACT are at significantly higher risk of adverse social and perinatal outcomes even when compared with mothers and infants exposed to other drugs of dependency. Increased vigilance for amphetamine exposure is recommended due to a high prevalence of use, especially in Australia, as a recreational drug. (Source: Archives of Disease in Childhood - Fetal and Neonatal Edition) Conclusions These findings provide strong evidence that morphine is rewarding in the C57 genotype and not in the DBA genotype. Understanding their relative susceptibility is important given the prominence of these genotypes in candidate gene identification and gene mapping. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1732-zAuthors Greg I. Elmer, University Maryland Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine Maple and Locust Sts Baltimore MD 21228 USAJeanne O. Pieper, NIDA Intramural Research Program, Behavioral Neuroscience Section Baltimore MD 21224 USALindsey R. Hamilton, NIDA Intramural Research Program, Behavioral Neuroscience Section Baltimore MD 21224 USARoy A. Wise, NIDA Intramural Re... A new model of the disrupted latent inhibition in C57BL/6J mice after bupropion treatment Conclusions Efficacy of rolipram but not antipsychotics to reverse the effects of bupropion suggests novel cAMP-dependent and D2 receptor-independent mechanisms of the bupropion-induced LI deficit. Further detailed biochemical analysis of bupropion-induced LI deficit might be a fruitful approach in developing new antipsychotics. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1749-3Authors Tatiana Lipina, Mount Sinai Hospital Samuel Lunenfeld Research Institute 600 University Avenue Toronto ON Canada M5G 1X5John Roder, Mount Sinai Hospital Samuel Lunenfeld Research Institute 600 University Avenue Toronto ON Canada M5G 1X5 Journal PsychopharmacologyOnline ISSN 1432-2072Print ISSN 0033-3158 (Source: Psychopharmacology) Conclusions Both the affective properties of intra-BLA CART 55–102 and its ability to either facilitate or block AMPH reward are dose dependent. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1748-4Authors David J. Rademacher, Rosalind Franklin University of Medicine and Science, Chicago Medical School Department of Cellular and Molecular Pharmacology 3333 Green Bay Road North Chicago IL 60064 USAElyse M. Sullivan, Rosalind Franklin University of Medicine and Science, Chicago Medical School Department of Cellular and Molecular Pharmacology 3333 Green Bay Road North Chicago IL 60064 USADavid A. Figge, Rosalind Franklin University of Medicine and Science, Chicago Medical School Department of Cellular and Molecular Pharmacology 3333 Gr... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Nociceptin/orphanin FQ (N/OFQ), an endogenous peptide agonist of the opioid N/OFQ receptor, has been implicated in the regulation of energy balance. In the present study, we have used immunohistochemistry to investigate the cellular localisation and colocalisation of N/OFQ-immunoreactive cell bodies in hypothalamic regions containing neurones producing orexigenic or anorexigenic transmitters. In colchicine-treated rats, N/OFQ immunoreactivity was demonstrated in many cell bodies of the arcuate nucleus (Arc), paraventricular nucleus (PVN) and lateral hypothalamic area (LHA). Double-labelling revealed that N/OFQ was present in some neurones located in the ventrolateral part of the Arc producing pro-opiomelanocortin, as shown by the presence of the anorexigenic peptides [alpha]-melanocyte-sti... This study examined the effect of prolonged food restriction, common in humans trying to lose body weight on expression of orexigenic and anorexigenic neuropetides genes and on malonyl-CoA content in rat whole hypothalamus.We observed an increase of NPY and AgRP mRNA levels in hypothalamus of rats kept on 30days-long food restriction (50% of the amount of food consumed by controls). Simultaneously, a decrease of CART and POMC mRNA levels occurred. Refeeding caused a decrease in NPY and POMC mRNA levels without effect on AgRP and CART mRNA. Surprisingly, both prolonged food restriction and food restriction/refeeding caused the increase of malonyl-CoA level in whole hypothalamus. In contrast, fasting for 24h caused the decrease of malonyl-CoA level, which was associated with the up-regulatio... Genome-wide census and expression profiling of chicken neuropeptide and prohormone convertase genes Abstract: Neuropeptides regulate cell-cell signaling and influence many biological processes in vertebrates, including development, growth, and reproduction. The complex processing of neuropeptides from prohormone proteins by prohormone convertases, combined with the evolutionary distance between the chicken and mammalian species that have experienced extensive neuropeptide research, has led to the empirical confirmation of only 18 chicken prohormone proteins. To expand our knowledge of the neuropeptide and prohormone convertase gene complement, we performed an exhaustive survey of the chicken genomic, EST, and proteomic databases using a list of 95 neuropeptide and 7 prohormone convertase genes known in other species. Analysis of the EST resources and 22 microarray studies offered a compr... Ecstasy Mimics: The NYC off-white Obama logo tablets contain the real stuff A recent post by Richard Metzger on Brand X site questions whether the widely reported samples of ecstasy tablets shaped like President Obama’s head actually contained the drug (MDMA). He mentioned a recent seizure of this product in North Carolina that — upon analysis by GC/MS — was shown to cotain BZP (benzylpiperazine), TFMPP (trifluoromethylphenylpiperazine) and caffeine. However, his reporting was incomplete. The August 2009 issue of DEA Microgram Bulletin described seizure in New York City of two off-white Obama tablets that did contain MDMA — in addition to BZP, TFMPP, procaine, and caffeine. The notice did not list the quantitative composition of the tablets. What about the other ingredients? BZP is a sympathomimetic stimulant, often used to mimic am... Conclusion: The study confirmed that the functions of specific brain regions underlying cognitive control are significantly impaired in patients of drug addiction. This impairment was significantly related to type of substance, duration of use and number of hospitalization and may contribute to most of behavioral disturbances found in addicts and need much attention during tailoring of treatment programs. (Source: Behavioral and Brain Functions) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. We describe the pharmacological and pharmacokinetic profile of SCH 486757, a nociceptin/orphanin FQ peptide (NOP) receptor agonist that has recently entered human clinical trials for cough. SCH 486757 selectively binds human NOP receptor (Ki=4.6+/-0.61 nM) over classical opioid receptors. In a guinea pig capsaicin cough model, SCH 486757 (0.01 - 1mg/kg) suppressed cough at 2, 4, and 6 hours post oral administration with a maximum efficacy occurring at 4hrs equivalent to codeine, hydrocodone, dextromethorphan and baclofen. The antitussive effects of SCH 486757 (3.0mg/kg, p.o.) was blocked by the NOP receptor antagonist J113397 (12mg/kg, i.p.) but not by naltrexone (10mg/kg, p.o.). SCH 486757 does not produce tolerance to its antitussive activity after a 5day BID dosing regimen. After acute ... Authors: Garrido EM, Garrido JM, Milhazes N, Borges F, Oliveira-Brett AM Amphetamine and amphetamine-like drugs are popular recreational drugs of abuse because they are powerful stimulants of the central nervous system. Due to a dramatic increase in the abuse of methylenedioxylated derivatives, individually and/or in a mixture, and to the incoherent and contradictory interpretation of the electrochemical data available on this subject, a comprehensive study of the redox properties of amphetamine-like drugs was accomplished. The oxidative behaviour of amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) was studied in different buffer systems by cyclic, differential pulse and square-wave voltammetry using a glassy carbon electro... J. Neurochem. (2010) The anti-parkinsonian drug, rasagiline [N-propargyl-1-(R)-aminoindan; Azilect®], is a secondary cyclic benzylamine and indane derivative, which provides irreversible, potent monoamine oxidase-B (MAO-B) inhibition and possesses neuroprotective and neurorestorative activities. A prospective clinical trial has shown that rasagiline confers significant symptomatic improvement and demonstrated alterations in Parkinson's disease progression. Rasagiline is primarily metabolized by hepatic cytochrome P-450 to form its major metabolite, 1-(R)-aminoindan, a non-amphetamine, weak reversible MAO-B inhibitor compound. Recent studies indicated the potential neuroprotective effect of 1-(R)-aminoindan, suggesting that it may contribute to the overall neuroprotective and antiapoptotic... The dopamine D2 receptor (DRD2) appears to be involved in impulsive behaviors, and particularly in behavioral inhibition. We sought to determine whether inhibition and impulsivity were related to genetic polymorphisms in the DRD2 gene (DRD2) in healthy volunteers (N = 93). Participants received placebo or d-amphetamine in random order. They performed the stop task, measuring behavioral inhibition, and rated their mood states on each session. They also completed the Zuckerman–Kuhlman Personality Questionnaire, including an Impulsivity subscale. We investigated the association between 12 single nucleotide polymorphisms (SNPs) and haplotypes in DRD2 and stop task performance in the nondrug (i.e., placebo) session and on the personality measure of impulsivity. We secondarily evaluated the DR... Mixing Pleasures: Review of the effects of drugs on sex behavior in humans and animal models. Authors: Frohmader KS, Pitchers KK, Balfour ME, Coolen LM Drugs of abuse act on the brain circuits mediating motivation and reward associated with natural behaviors. There is ample evidence that drugs of abuse impact male and female sexual behavior. First, the current review discusses the effect of drugs of abuse on sexual motivation and performance in male and female humans. In particular, we discuss the effects of commonly abused drugs including psychostimulants, opiates, marijuana/THC and alcohol. In general, drug use affects sexual motivation, arousal, as performance, and is commonly associated with increased sexual risk behaviors. Second, studies on effects of systemic administration of drugs of abuse on sexual behavior in animals are reviewed. These studies analyze effects on sex... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Missouri government plots undercover sting operations against families selling raw milk (NaturalNews) Imagine being watched by two undercover cops as you engage in an illicit deal in a deserted parking lot. The buyer hesitantly hands you some cash. You flash a look over your shoulder, just to make sure the coast is clear, then you hand over the contraband. Neither of you says a word. You just nod, acknowledging the deal is done, then you head back to your car and buckle up for the drive home.But before you can even put the car into drive, a screeching formation of police cars, surrounds you, sirens wailing. Armed officers leap from their vehicles, guns drawn and sunglasses glaring. "Come out with your hands up!" they shout.You slowly open the driver's door of your car and inch out of your seat with both hands raised in surrender, cowering behind the open door. "What did I do,... WHAT MAKES TIGERS JUMP?Oxytocin, Dopamine, and Phenylethylamine Tiger, tiger, burning brightIn the forests of the nightWhat immortal hand or eyeCould frame thy fearful symmetry? From: The TigerWilliam Blake (1757-1827) ... Conclusions These data suggest that dopaminergic systems in the NAc may play important roles in p-OHA-induced locomotor activity in rodents. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1734-xAuthors Hiroshi Onogi, Tohoku Pharmaceutical University Department of Pharmacology 4-4-1 Komatsushima, Aoba-ku Sendai 981-8558 JapanMasato Hozumi, Tohoku Pharmaceutical University Department of Pharmacology 4-4-1 Komatsushima, Aoba-ku Sendai 981-8558 JapanOsamu Nakagawasai, Tohoku Pharmaceutical University Department of Pharmacology 4-4-1 Komatsushima, Aoba-ku Sendai 981-8558 JapanYuichiro Arai, Tokyo Ariake University of Medical and Health Sciences Tokyo 135-0063 JapanSeiichiro Ishigaki, Showa University Department of Neurology, School of Medic... Repeated use of the drug popularly known as "ecstasy" significantly raises the risk of developing sleep apnea in otherwise healthy young adults with no other known risk factors for the sleep disturbance, a new study suggests. The finding is the latest highlighting the potential dangers of the amphetamine-style chemical, currently used illegally by millions of people in the United States. (Source: ScienceDaily Headlines) Ecstasy Use May Lead to Sleep Apnea-11/25/09 Repeated use of the drug popularly known as “ecstasy” significantly raises the risk of developing sleep apnea in otherwise healthy young adults with no other known risk factors for the sleep disturbance, a new study by Johns Hopkins scientists suggests. The finding is the latest highlighting the potential dangers of the amphetamine-style chemical, currently used illegally by millions of people in the United States. (Source: Johns Hopkins Medicine News) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Ecstasy Use May Lead To Sleep Apnea Repeated use of the drug popularly known as "ecstasy" significantly raises the risk of developing sleep apnea in otherwise healthy young adults with no other known risk factors for the sleep disturbance, a new study by Johns Hopkins scientists suggests. The finding is the latest highlighting the potential dangers of the amphetamine-style chemical, currently used illegally by millions of people in the United States... (Source: Health News from Medical News Today) Updated Date: Dec 3, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) [11C]-(+)-PHNO is a new dopamine D2/3 receptor agonist radiotracer which has been successfully used to measure D2/3 receptor availability in experimental animals and man. Here we report in vivo evaluation in the rat of the biodistribution, metabolism, specificity, selectivity, and dopamine sensitivity of carbon11-labeled PHNO ([11C]-3-PHNO) produced by an alternative radiochemical synthesis method. [11C]-3-PHNO showed rapid metabolism and clearance from most peripheral organs and tissues. [11C]-3-PHNO, but not its polar metabolite, readily crossed the blood-brain barrier and showed high levels of uptake in the D2/3-rich striatum. Pretreatment with unlabeled PHNO and the D2/3 receptor antagonist raclopride indicated that binding in the striatum was specific and selective to D2/3 receptors. ... Conclusions. Relative to gold standard ex vivo results, microPET estimates of DMFP BPND were unbiased, whereas FP BPND in striatum was substantially underestimated. Both tracers proved suitable for revealing pharmacologically evoked changes in competition at D2/3-receptors in striatum of living mice. Synapse 64:313-322, 2010. © 2009 Wiley-Liss, Inc. (Source: Synapse) This study was performed to characterize the intestinal transport of beta-phenylethylamine (PEA). Uptake of [(14)C]PEA into Caco-2 cells was Na(+)-independent but strongly stimulated by an outside directed H(+) gradient. At extracellular pH 7.5, the concentration-dependent uptake of PEA was saturable with kinetic parameters of 2.6 mM (K(t)) and 96.2 nmol/min per mg of protein (V(max)). Several biogenic amines such as harmaline and N-methylphenylethylamine as well as cationic drugs such as phenelzine, tranylcypromine, D,L-amphetamine, methadone, chlorphenamine, diphenhydramine, and promethazine strongly inhibited the [(14)C]PEA uptake with K(i) values around 1 mM. Tetraethylammonium, N-methyl-4-phenylpyridinium and choline had no effect. We also studied the bidirectional transepithelial tra... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Neonatal quinpirole treatment to rats produces long-term increases in D2 receptor sensitivity that persists throughout the animal's lifetime, a phenomenon referred to as D2 priming. Male and female Sprague-dawley rats were administered quinpirole (1 mg kg-1) or saline from postnatal days (P)1-11. At P60, all animals were given an injection of quinpirole (100 [mu]g kg-1), and results showed that rats neonatally treated with quinpirole demonstrated enhanced yawning in response to quinprole, verifying D2 receptor priming because yawning is a D2 receptor mediated event. Beginning 1-3 days later, locomotor sensitization was tested through administration of d-amphetamine (1 mg kg-1) or saline every other day over 14 days, and horizontal activity and turning behavior were analyzed. Findings indic... Dopamine-induced changes in neural network patterns supporting aversive conditioning. Authors: Diaconescu AO, Menon M, Jensen J, Kapur S, McIntosh AR The aim of the present paper is to assess the effects of altered dopamine (DA) transmission on the functional connectivity among brain regions mediating aversive conditioning in humans. To this aim, we analyzed a previous published data set from a double-blind design combined with functional magnetic resonance imaging (fMRI) recordings in which healthy volunteers were randomly assigned to one of three drug groups: amphetamine (an indirect DA agonist), haloperidol (DA D2 receptor antagonist), and placebo. Participants were exposed to an aversive classical conditioning paradigm using cutaneous electrical stimulation as the unconditioned stimulus (US), and visual cues as the conditioned stimuli (CS) where one colour (CS+) was... Better Living through Cognitive Dissonance Misinterpreting the message of cognitive dissonance ruins marriages, a fact that totally eludes marriage therapists and relationship authors who promote "getting your needs met."Cognitive dissonance is the discomfort of self-image colliding with reality. Such collisions are inevitable, as self-image tends to be based on values - what is most important to you - while behavior is routinely directed at short-term comfort, pleasure, and utilitarian goals.The common cognitive dissonance in intimate relationships is:I am a loving and compassionate person.Yet I am not loving and compassionate to you at this moment.The way we resolve cognitive dissonance helps determine health and well being. The following choice gives you the best chance of achieving a solid and authentic sense of self while impr... Conclusion: The obtained results showed cannabinoids and amphetamine derivatives to be the most frequent whereas opium alkaloids, barbiturates and benzodiazepines rather rare psychoactive drugs found in the tested blood samples of the drivers involved in the road accidents. The authors suggest screening psychoactive drugs not only in drivers involved in road accidents but also those put through the routine road check procedures. While giving opinions on the influence of the above mentioned drugs on the psychophysical efficiency of road traffic users, drugs and compounds which are not subject to legal control but have an effect on the human psychomotor efficiency and thus, enhance the risk of the road accident should be also taken into account. (Source: Forensic Science International Supple... This study also highlights some pitfalls of the DRUID repression policy currently followed by France, especially interpretation of low concentrations of drugs of abuse (in our study, 28.2% of drivers found positive for cannabis at the immunoassay screening had blood THC levels (Source: Forensic Science International Supplement Series) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. The toxicological challenges in the European research project DRUID Abstract: Within the epidemiological studies of the integrated European research project DRUID (Driving Under the Influence of Drugs, alcohol and medicines), 13 laboratories from across Europe will analyse whole blood, oral fluid (OF) or urine from the general driving population and injured drivers. To ensure the comparability of toxicological results from the different studies, the collection of samples, analytical methods, target analytes and analytical cut-offs have been standardized for all laboratories involved.Target analytes were selected based on suspected impairing effects and prevalence. Twenty-three drugs are included in the ‘core list’ for which analysis is mandatory: ethanol, amphetamine, MDMA, MDA, MDEA, methamphetamine, cocaine, benzoylecgonine, THC, THC-COOH, 6-acetylmo... A high-performance liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method has been developed and validated for the determination of 19 drugs of abuse and metabolites and used in whole blood. The following compounds were included: amphetamine, m... (Source: SafetyLit: All (Unduplicated)) Are attention lapses related to d-amphetamine liking? Conclusion The findings suggest that participants who exhibit impaired attention may be less sensitive to stimulant-induced euphoria. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1719-9Authors Michael McCloskey, Temple University Department of Psychology 1701 North 13th Street Philadelphia PA 19122 USAAbraham A. Palmer, University of Chicago Department of Psychiatry and Behavioral Neuroscience Chicago IL 60637 USAHarriet de Wit, University of Chicago Department of Psychiatry and Behavioral Neuroscience Chicago IL 60637 USA Journal PsychopharmacologyOnline ISSN 1432-2072Print ISSN 0033-3158 (Source: Psychopharmacology) The impact of the circadian timing system upon behavior and physiology is pervasive, and previous evidence suggests a circadian modulation of drug-seeking behavior and responsiveness to drugs of abuse. To further characterize daily rhythms in reward and to extend these observations to natural reinforcers, diurnal variation in the rewarding value of sex and systemic amphetamine was assessed via the conditioned place preference paradigm. To identify potential mechanisms for rhythmicity in reward, levels of tyrosine hydroxylase (TH) and core clock proteins (Period1 and Bmal1) were examined across the day in the ventral tegmental area (VTA) and the nucleus accumbens (NAcc). During an initial training period, male rat sexual performance varied diurnally with a nadir near the light-to-dark trans... Dysregulation of intracellular dopamine stores revealed in the R6/2 mouse striatum J. Neurochem. (2009) 10.1111/j.1471-4159.2009.06501.x Huntington's disease (HD) is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine (DA) in striatal brain slices from HD model R6/2 mice. When applying stimulus trains of 120 pulses, evoked DA release in wild-type (WT) slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool DA levels, amphetamine-induced DA efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-p-tyrosine. Slices from 12-week-old R6/2 mice released less DA than slices from WT mice, while no difference was noted in s... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Abstract: A gas chromatography–mass spectrometry (GC–MS) method was developed and validated for the simultaneous qualification and quantification of methamphetamine (MA), amphetamine (AP), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-amphetamine (MDA), ketamine (KET) and norketamine (NKT) in fingernails. Fingernail samples (20mg) were washed with distilled water and methanol, digested with 1.0M sodium hydroxide at 95°C for 30min, and then extracted with ethyl acetate. Extract solutions were evaporated to dryness, derivatized using heptafluorobutyric anhydride (HFBA) at 60°C for 30min, and analyzed by GC–MS. The linear ranges were 0.1–20.0ng/mg for AP, MDMA and NKT, 0.2–20.0ng/mg for MA and MDA, and 0.4–20.0ng/mg for KET, with the coefficients of determi... In this study, we examined locomotor responses of male and female juvenile and adult rats to a dose range of amphetamine. We also measured dopamine receptor and monoamine transporter densities in adult brain. Results Female DVD-deficient adult rats displayed an enhanced sensitivity to amphetamine-induced locomotion, an increased dopamine transporter density in the caudate–putamen and increased affinity in the nucleus accumbens compared with control females. By contrast, there were no differences between control and DVD-deficient male rats. Discussion Taken together, this suggests an alteration in the development of the dopamine system and on dopamine-mediated behaviors in female DVD-deficient rats, and this may be relevant to the underlying neurobi... Authors: Bjørk MK, Nielsen MK, Markussen LO, Klinke HB, Linnet K A high-performance liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method has been developed and validated for the determination of 19 drugs of abuse and metabolites and used in whole blood. The following compounds were included: amphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, methamphetamine, cocaine, benzoylecgonine, morphine, 6-acetylmorphine, codeine, methadone, buprenorphine, norbuprenorphine, ketobemidone, tramadol, O-desmethyltramadol, zaleplone, zolpidem, and zopiclone. The sample pretreatment consisted of solid-phase extraction using mixed-mode columns (Isolute Confirm HCX). Deuterated analogues were used as internal standards for all analyte... Conclusions Methamphetamine improved verbal fluency and MDMA adversely affected fluency. This pattern of effects is consistent with the effects of these drugs on functioning in other cognitive domains. In general, methamphetamine effects on speech were inconsistent with effects popularly attributed to this drug, while MDMA-related effects were in agreement with some anecdotal reports and discordant with others. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1715-0Authors Gina F. Marrone, New York State Psychiatric Institute Division of Substance Abuse 1051 Riverside Dr., Unit 120 New York NY 10032 USAJennifer S. Pardo, Columbia University Department of Psychology, Barnard College New York NY USARobert M. Krauss, Columbia University ... Shire announces publication of open-label study on coadministration of INTUNIV with stimulants (Porter Novelli) Shire plc announced new study results on INTUNIV published in the October Journal of Child and Adolescent Psychopharmacology. In this open-label safety study, there was no evidence of unique adverse effects with the combination of INTUNIV and amphetamine or methylphenidate relative to what was observed with either medication alone. The open-label study also assessed improvement of ADHD symptoms using the ADHD-RS-IV. (Source: EurekAlert! - Social and Behavioral Science) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusions: Lithium and carbamazepine preferentially inhibit AC5, albeit via different mechanisms. Lithium competes with Mg2+, which is essential for AC activity; carbamazepine competes for AC's catechol-estrogen site. Antidepressant-like behavior of AC5 knockout mice in the forced-swim test supports the notion that AC5 inhibition is involved in the antidepressant effect of lithium and carbamazepine. The effect of lithium and carbamazepine to lower cAMP formation in AC5-rich dopaminergic brain regions suggests that D1-dopamine receptors in these regions are involved in the antidepressant effect of mood stabilizers. (Source: Bipolar Disorders) Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are c... (Source: SafetyLit: All (Unduplicated)) Conclusion: PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS. (Source: BMC Neuroscience - Latest articles) Authors: Postigo C, López de Alda MJ, Barceló D Drugs of abuse and their metabolites have been recently recognized as environmental emerging organic contaminants. Assessment of their concentration in different environmental compartments is essential to evaluate their potential ecotoxicological effects. It also constitutes an indirect tool to estimate drug abuse by the population at the community level. The present work reports for the first time the occurrence of drugs of abuse and metabolites residues along the Ebro River basin (NE Spain) and also evaluates the contribution of sewage treatment plants (STPs) effluents to the presence of these chemicals in natural surface waters. Concentrations measured in influent sewage waters were used to back calculate drug usage at the co... Authors: Gonkowski S, Burliński P, Skobowiat C, Majewski M, Arciszewski MB, Radziszewski P, Całka J The aim of the present study was to investigate the number of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) nerve structures in the large intestine of juvenile pigs. The distribution pattern of CART-LI structures was studied by immunohistochemistry in the circular muscle layer, myenteric (MP), outer submucous (OSP) and inner submucous plexus (ISP) as well as in the mucosal layer of six regions of the large bowel: caecum, centripetal and centrifugal turns of the proximal colon, transverse colon, descending colon and rectum. CART-LI neural structures were observed in all gut fragments studied. CART-LI nerve fibres were numerous within the circular ... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. This study explores primarily the role of the activity of monoamine oxidase B (MAOB) in the regulation of glutamic acid decarboxylase(67) (GAD(67)) expression in distinct layers of main olfactory bulb (OlfB), which links the limbic system. Moreover, the response of GAD(67) was investigated to amphetamine perturbation in the absence of MAOB activity. Immunocytochemical analysis was performed on OlfB sections prepared from the adult wild type (WT) and the MAOB gene-knocked-out (KO) mice after receiving repeated intraperitoneal injections (two doses per day, total seven doses) of saline or amphetamine, 5 mg/kg. The levels of the GAD(67) immunoreactivity were approximate 25 and 38% lower in respective glomerular (GloL) and mitral cell layers (ML) of saline-treated KO mice than that of WT, wher... Abstract: This paper presents a rapid and sensitive method for the determination and chiral separation of amphetamines and related designer drugs in hair samples. The substances are extracted from hair matrix by a 30min treatment with a saturated carbonate buffer at pH 10 under ultrasonication. A commercial chiral derivatizing agent, trifluoroacetyl-prolyl chloride, is then added to the solution that is directly extracted with hexane and subsequently analyzed by GC/MS in SIM mode. R and S isomers of amphetamine, methamphetamine, MDA, MDMA and MDEA can be separated and detected with a limit of detection of 0.1ng/mg for amphetamine, methamphetamine and MDA, and of 0.2ng/mg for MDMA and MDEA. The method was then applied to 12 samples from suspected amphetamines abusers, showing the presence o... Sodium-chloride coupled neurotransmitter transporters achieve reuptake of their physiological substrate by exploiting the pre-existing sodium-gradient across the cellular membrane. This terminates the action of previously released substrate in the synaptic cleft. However, a change of the transmembrane ionic gradients or specific binding of some psychostimulant drugs to these proteins, like amphetamine and its derivatives, induce reverse operation of neurotransmitter:sodium symporters. This effect eventually leads to an increase in the synaptic concentration of non-exocytotically released neurotransmitters [and [ndash] in the case of the norepinephrine transporters, underlies the well-known indirect sympathomimetic activity]. While this action has long been appreciated, the underlying mecha... Stereoselectivity in the human metabolism of methamphetamine CONCLUSIONS The metabolism of MA is enantioselective, with formation of AMP having the highest isomer selectivity. A greater percentage of MA is converted to pOH-MA (8[ndash]11%) than AMP (2[ndash]7%). The formation of pOH-MA was less affected by the MA enantiomer administered, suggesting that urine pOH-MA may be a more stable biomarker of MA metabolism. (Source: British Journal of Clinical Pharmacology) David Nutt may set up new drugs body Scientist removed for views on cannabis says government's advisory council is fatally flawed and should be independentThe government's drug advice body is "fatally flawed" and should be reconstituted as an independent organisation along the lines of the Bank of England, according to former government drugs adviser David Nutt, who was sacked last week in a row over the classification of cannabis. Nutt said that if the Advisory Council on the Misuse of Drugs (ACMD) was not given more autonomy in future he would consider setting up an alternative committee to provide independent advice on drugs."Unless this issue is resolved properly, you're going to have to have an independent group. I know several members of the council will join me if things aren't resolved next Tuesday," he said. "It's ob... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. ARTICLE: Case-control Study of a Gastroschisis Cluster in Nevada Conclusions These findings add strength to the hypothesis that use of methamphetamine and related drugs is a risk factor for gastroschisis and raise questions about the risks associated with infections. (Source: Archives of Pediatrics) Case-control Study of a Gastroschisis Cluster in Nevada [Article] Conclusions These findings add strength to the hypothesis that use of methamphetamine and related drugs is a risk factor for gastroschisis and raise questions about the risks associated with infections. (Source: Archives of Pediatrics) Early postnatal behavioral changes in the Mecp2-308 truncation mouse model of Rett syndrome In a mouse model of Rett syndrome (RTT) which expresses a truncated form of methyl-CpG-binding protein 2 (Mecp2) gene (Mecp2-308), we performed a neurobehavioral evaluation across the life span, starting from soon after birth till adulthood. A focus was made on those developmental phases and behavioral domains which have not been previously investigated. The results evidenced subtle anomalies on postnatal days (pnds) 3 to 9 (so-called presymptomatic phase) in spontaneous movements by hemizygous neonatal male mice. Specifically as early as pnd 3, mutant pups exhibited more intense curling and more side responses and on pnd 9 more pivoting and head rising behaviors than wild type (wt) littermates. A significant decrease in ultrasonic vocalization rate, also emerged in Mecp2-308 pups. The sam... Morbidity involving the hallucinogenic designer amines MDA and 2C-I. This report demonstrates the utility of testing for a wider menu of compounds using LC-MS/MS in order to better characterize the prevalence and toxicities of novel amines such as 2C-I. PMID: 19878416 [PubMed - in process] (Source: Journal of Forensic Sciences) Contribution of early environmental stress to alcoholism vulnerability Abstract: The most problematic aspects of alcohol abuse disorder are excessive alcohol consumption and the inability to refrain from alcohol consumption during attempted abstinence. The root causes that predispose certain individuals to these problems are poorly understood but are believed to be produced by a combination of genetic and environmental factors. Early environmental trauma alters neurodevelopmental trajectories that can predispose an individual to a number of neuropsychiatric disorders, including substance abuse. Prenatal stress (PNS) is a well-established protocol that produces perturbations in nervous system development, resulting in behavioral alterations that include hyperresponsiveness to stress, novelty, and psychomotor stimulant drugs (e.g., cocaine, amphetamine). Moreov... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cardiovascular risk in ADHD pharmacotherapy Pharmacotherapy, namely the stimulant medications methylphenidate (MPH) and amphetamine (MAS) and the nonstimulant medication atomoxetine (Strattera), is the recommended treatment for attention-deficit/hyperactivity disorder (ADHD). (Source: Modern Medicine Contemporary Pediatrics) Conclusions: All DA releasing agents tested, and some DAT-inhibiting agents, produced RHS at equal wake-promoting doses. Thus amphetamine-like DA release appears sufficient for inducing RHS, but additional properties (pharmacologic and/or pharmacokinetic) evidently underlie RHS of other DAT inhibitors. Enhancing wake while mitigating RHS can be achieved by combining DAT-inhibiting and DA-releasing agents. Keywords: Sleep/wake, dopamine transporter, amphetamine, hypersomnolence, pharmacokinetic, rat (Source: Sleep) Role of hypoleptinemia during cold adaptation in Brandt's voles (Lasiopodomys brandtii) Brandt's voles Lasiopodomys brandtii exhibit large increases in nonshivering thermogenesis to cope with chronic cold exposure, resulting in compensatory hyperphagia and fat mobilization. These physiological events are accompanied by a remarkable reduction in serum leptin levels. However, the role of hypoleptinemia in cold adaptation in this species is still unknown. In the present study, we tested the hypothesis that hypoleptinemia contributes to increases in food intake and brown adipose tissue (BAT) thermogenesis by modifying hypothalamic neuropeptides in cold-exposed Brandt's voles. Adult male voles were transferred to 5°C for 28 days. Accompanied by a decrease in serum leptin levels, hypothalamic agouti-related protein (AgRP) mRNA levels were significantly increased, but there were... Updated Date: Oct 30, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) The molecular biology of addictive drugs This article reviews those experiments that have studied drug-induced alterations in gene transcription. Ethanol has diverse effects on the amounts of messenger RNA molecules within the central nervous system. Ion channels, neuropeptides, membrane receptors, and immediate early genes represent several regulated mRNAs. The effects are selective, however, as many other specific products are not altered. Evidence for a genetic predisposition to ethanol use reinforces the importance of the genotype. Opioids, cocaine, and amphetamine also affect gene transcription. Messenger RNAs studied have included many of those demonstrated to be altered by alcohol use. Interestingly, use of any of these drugs alters the expression of immediate early genes. These genes may represent an initia... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Methanandamide blocks amphetamine-induced behavioral sensitization in rats. Authors: Rasmussen BA, Unterwald EM, Rawls SM Methanandamide acts at targets which modulate amphetamine-induced behaviors. Therefore, we investigated methanandamide effects on the acute hyperactivity produced by a single injection of amphetamine and behavioral sensitization induced by repeated amphetamine exposure in rats. Methanandamide (5mg/kg, i.p.) did not affect basal locomotor or stereotypical activity. Methanandamide (5mg/kg, i.p.) pretreatment did not alter the acute increase in locomotor or stereotypical activities produced by acute amphetamine (2mg/kg, i.p.). For chronic studies, rats injected with amphetamine (2mg/kg, i.p.) once daily for 3 consecutive days were then challenged with amphetamine (2mg/kg, i.p.) 5days later. Expression of locomotor sensitization was blocked whe... Conclusions: The UPLC-MS/MS method makes it possible to detect all 29 analytes in 1 chromatographic run (15 min), including -9-tetrahydrocannabinol and benzoylecgonine, which previously have been difficult to incorporate into multicomponent methods. (Source: Clinical Chemistry) Abstract: A study of Section 4 RTOA cases submitted to the SPSA forensic science laboratory in Edinburgh over a 12year period was carried out. The main aims of the study were to identify the most frequently encountered drugs and to determine if there were any major drugs trends from the data collected. Three groups of cases from 1996 to 2000 (102 cases), 2003 (26 cases) and 2008 (295 cases) were examined. The large increase in submissions was mainly due to the introduction of SPSA, whereby the laboratory began to carry out the analysis for all criminal and RTOA cases in Scotland. The preliminary results for the 8 drug groups (amphetamine and related compounds, benzodiazepines, cannabinoids, cocaine, methadone, methylamphetamine and related compounds, morphine and opiates) identified a num... Conclusions. This study found that the implantation of CTX0E03 human neural stem cells in rats after MCAO stroke promoted significant behavioral recovery depending on cell dose. The authors propose a paracrine trophic mechanism, which is triggered early after CTX0E03 cell implantation, and which in turn targets restoration of neurogenesis in the SVZ of MCAO rats. (Source: Neurorehabilitation and Neural Repair) Shire Announces New Data on Pharmacokinetics of Vyvanse Findings show intranasal administration of Vyvanse did not result in a greater exposure of d-amphetamine, the active medication in Vyvanse, compared with oral administration PHILADELPHIA – October 22, 2009 – Shire plc (LSE: SHP, NASDAQ:... (Source: Drugs.com - Clinical Trials) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Review: limited evidence to support pharmacological therapy for amphetamine withdrawal (Source: Evidence-Based Mental Health) Amphetamine Use In Adolescence May Impair Adult Working Memory Rats exposed to high doses of amphetamines at an age that corresponds to the later years of human adolescence display significant memory deficits as adults -- long after the exposure ends, researchers report. (Source: ScienceDaily Headlines) Adult Working Memory May Be Impaired By Amphetamine Use In Adolescence Rats exposed to high doses of amphetamines at an age that corresponds to the later years of human adolescence display significant memory deficits as adults - long after the exposure ends, researchers report. The declines in short-term or "working" memory are most pronounced when the rats are exposed during adolescence, rather than as adults, the researchers found... (Source: ADHD News From Medical News Today) Adult Working Memory May Be Impaired By Amphetamine Use In Adolescence Rats exposed to high doses of amphetamines at an age that corresponds to the later years of human adolescence display significant memory deficits as adults - long after the exposure ends, researchers report. The declines in short-term or "working" memory are most pronounced when the rats are exposed during adolescence, rather than as adults, the researchers found. (Source: Health News from Medical News Today) Vyvanse Capsules CII administration through 2 routes demonstrated similar pharmacokinetic profile (Porter Novelli) Shire PLC announced new data about the pharmacokinetics of its attention-deficit/hyperactivity disorder medication, Vyvanse (lisdexamfetamine dimesylate) Capsules CII, which showed that Vyvanse provided similar concentrations of its active medication in the blood when administered either intranasally or when administered orally. Specifically, the overall rate and extent of exposure to d-amphetamine, the active medication in Vyvanse, was similar in healthy adults whether they received the drug as a solution through the nose or orally as a capsule. (Source: EurekAlert! - Social and Behavioral Science) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Is A Hook-Up Culture Going To Help Us Get There? What happens (in the brain) when we experience the PASSION associated with a hook-up? Obviously, LOTS --- since such an experience will involve the stimulation of no fewer than several hundred thousand brain cells. But more specifically, what bio-chemical concoction (love potion?) is brewing? Some people may have heard of PEA (Phenylethylamine) --- this is an amphetamine-like chemical released by the brain during periods of passionate in-love-ness. [You would probably not be surprised to find that there are currently several pharmaceutical companies attempting to mimic PEA. It would be the greatest love drug (not to mention money-maker) since Viagra. Can you imagine the shift in couples’ therapy: “Go home, take 2 of these, go to bed, and simply ... Conclusions The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release amphetamine dispensing under pharmacist supervision is both feasible and safe. The increased retention in the dexamphetamine group, together with the general decreases in methamphetamine use, degree of dependence and withdrawal symptom severity, provide preliminary evidence that this may be an efficacious treatment option for methamphetamine dependence. (Source: Addiction) D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD. Authors: Fan X, Xu M, Hess EJ Low doses of psychostimulants produce beneficial behavioral effects in ADHD patients but the mechanisms underlying the response are not understood. Here we use the hyperactive mouse mutant coloboma to identify D2-like dopamine receptor subtypes that mediate the hyperactivity and response to amphetamine; we have previously demonstrated that D1-like dopamine receptors are not involved. Targeted deletion of the D2, but not the D3 or the D4, dopamine receptor in coloboma mice eliminated the hyperactivity; depleting D2 dopamine receptors also restored the excess dopamine overflow that may drive the hyperactivity to normal concentrations. Similar to its effects on ADHD patients, amphetamine reduced the hyperactivity of coloboma mice. The D2 dopamine receptor-sel... Restoration of amphetamine-induced locomotor sensitization in dopamine D1 receptor-deficient mice Conclusions D1 receptors were necessary for induction, but may not be necessary for expression of amphetamine-induced sensitization at low doses. The manifestation of amphetamine sensitization depended on the duration of treatment and length of the withdrawal period. Cholinergic–nicotinic stimulation restored amphetamine-induced sensitization in D1−/− mice. Enhanced basal expression of p-CREB in D1−/− mice may represent an adaptive mechanism related to lack of D1 receptors. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00213-009-1690-5Authors Mufida B. El-Ghundi, University of Toronto Department of Pharmacology Medical Sciences Building, 1 King’s College Circle Toronto ON Canada M5S 1A8Theresa Fan, University of Toronto Department... |