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Patrick C Dolder, Petra Strajhar, Patrick Vizeli, Alex Odermatt, Matthias E Liechti
RATIONALE: Amphetamines are used as medications but are also misused as cognitive enhancers by healthy subjects and may have additional effects on social cognition. METHODS: We investigated the acute effects of single, high, equimolar doses of D-amphetamine (40 mg) and lisdexamfetamine (100 mg) on social cognition and cognitive performance using a randomized, placebo-controlled, double-blind, cross-over design in 24 healthy volunteers. Effects on social cognition were assessed using the Facial Emotion Recognition Task (FERT), Multifaceted Empathy Test (MET), and Sexual Arousal Task (SAT)...
February 9, 2018: Psychopharmacology
Tara L White, Mollie A Monnig, Edward G Walsh, Adam Z Nitenson, Ashley D Harris, Ronald A Cohen, Eric C Porges, Adam J Woods, Damon G Lamb, Chelsea A Boyd, Sinda Fekir
Prescription psychostimulants produce rapid changes in mood, energy, and attention. These drugs are widely used and abused. However, their effects in human neocortex on glutamate and glutamine (pooled as Glx), and key neurometabolites such as N-acetylaspartate (tNAA), creatine (tCr), choline (Cho), and myo-inositol (Ins) are poorly understood. Changes in these compounds could inform the mechanism of action of psychostimulant drugs and their abuse potential in humans. We investigated the acute impact of two FDA-approved psychostimulant drugs on neurometabolites using magnetic resonance spectroscopy (1 H MRS)...
March 6, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ville Oinio, Mikko Sundström, Pia Bäckström, Johanna Uhari-Väänänen, Kalervo Kiianmaa, Atso Raasmaja, Petteri Piepponen
RATIONALE: Comorbidity with gambling disorder (GD) and alcohol use disorder (AUD) is well documented. OBJECTIVE: The purpose of our study was to examine the influence of genetic alcohol drinking tendency on reward-guided decision making behavior of rats and the impact of dopamine releaser D-amphetamine on this behavior. METHODS: In this study, Alko alcohol (AA) and Wistar rats went through long periods of operant lever pressing training where the task was to choose the profitable of two options...
February 9, 2018: Psychopharmacology
Joseph T Coyle, Darrick T Balu
The N-methyl-d-aspartate receptor (NMDAR) is unique in requiring two agonists to bind simultaneously to open its cation channel: the neurotransmitter, glutamate, and the coagonists, glycine, or d-serine. The Snyder laboratory was the first to clone serine racemase (SR), the enzyme that synthesizes d-serine, and to localize it immunocytochemically. Our laboratory has focused on the role of d-serine in brain disorders. Silencing the expression of SR, a risk gene for schizophrenia (SCZ), in mice (SR-/-), results in a phenotype that closely resembles SCZ including: cortical atrophy, reduced dendritic spine density and complexity, downregulation of parvalbumin-positive cortical GABAergic neurons, and cognitive impairments...
2018: Advances in Pharmacology
Ryan T Lacy, Hannah K Schorsch, Bridget P Austin
Diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) has risen drastically over the past 20 years in the United States and abroad. Amphetamine-based prescription stimulants are the most prescribed treatment for ADHD and the diversion of these drugs has also increased. Reports indicate 61% of individuals with an ADHD medication prescription have sold or shared their medication. Exposure to prescription stimulants, especially for those without an ADHD diagnosis, may increase susceptibility to drugs of abuse...
February 2018: Experimental and Clinical Psychopharmacology
S Ghazala, J Bilal, E Ross, B Kalb, I B Riaz, K L Herbst
BACKGROUND/AIM: Dercum disease is a rare disorder of painful subcutaneous adipose tissue masses typically presenting as a constellation of signs and symptoms affecting most organs including slow lymphatic flow and fatty liver. METHOD: The University of Arizona Institutional Review Board considered this report exempt after patient consent. Multislice, multisequence magnetic resonance imaging (MRI) of the abdomen and pelvis was performed before and after d-amphetamine, with and without intravenous gadolinium...
January 17, 2018: American Journal of Medicine
Mollie S Pester, Matthew G Kirkpatrick, Bree A Geary, Adam M Leventhal
While individual differences in reward sensitivity are believed to generalize across drugs and alternative rewards, this notion has received little empirical attention in human research. Here, we tested whether individual differences in the subjective rewarding effects of physical activity were associated with the subjective response to d-amphetamine administration. Healthy volunteers ( n=95; age 18-35 years) completed questionnaires measuring the self-reported pleasurable effects of physical activity and other covariates, and this was followed by two double-blind counterbalanced sessions during which they received either 20 mg oral d-amphetamine or placebo...
January 1, 2018: Journal of Psychopharmacology
W Gordon Frankle, Jennifer Paris, Michael Himes, N Scott Mason, Chester A Mathis, Rajesh Narendran
BACKGROUND: Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with D2/3 antagonist radiotracers, is the failure to provide information about D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it critical to understand the status of D2/3 HIGH receptors in SCH...
December 7, 2017: Biological Psychiatry
James MacKillop, Nicholas I Goldenson, Matthew G Kirkpatrick, Adam M Leventhal
Behavioral economic purchase tasks quantify drug demand (i.e. reinforcing value of a drug) and have been used extensively to assess the value of various drugs among current users. However, purchase tasks have been rarely used with unfamiliar drugs to address a compound's abuse liability, and the current study sought to validate the paradigm in this capacity. Using a double-blind placebo-controlled within-subjects drug challenge design, the study evaluated differential drug demand on an experimental drug purchase task for a 20 mg dose of oral D-amphetamine (versus placebo), a prototypic psychostimulant, in 98 stimulant-naïve participants...
January 5, 2018: Addiction Biology
Kristen Ward, Leslie Citrome
The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing...
February 2018: Expert Opinion on Drug Metabolism & Toxicology
Ana P Herrmann, Roberta Andrejew, Radharani Benvenutti, Clarissa S Gama, Elaine Elisabetsky
OBJECTIVE: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. METHODS: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg...
December 11, 2017: Revista Brasileira de Psiquiatria
Jennifer M Wright, Suelynn Ren, Annie Constantin, Paul B S Clarke
RATIONALE AND OBJECTIVES: Nicotine and D-amphetamine can strengthen reinforcing effects of unconditioned visual stimuli. We investigated whether these reinforcement-enhancing effects reflect a slowing of stimulus habituation and depend on food restriction. METHODS: Adult male rats pressed an active lever to illuminate a cue light during daily 60-min sessions. Depending on the experiment, rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg IP) and nicotine (0...
March 2018: Psychopharmacology
S F Lisboa, A C Issy, C Biojone, K Montezuma, V Fattori, E A Del-Bel, F S Guimarães, F Q Cunha, W A Verri, S R L Joca
Preclinical and clinical evidence suggests pro-inflammatory cytokines might play an important role in the neurobiology of schizophrenia and stress-related psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and it is widely expressed in brain regions involved in emotional regulation. Since IL-18 involvement in the neurobiology of mental illnesses, including schizophrenia, remains unknown, this work aimed at investigating the behavior of IL-18 null mice (KO) in different preclinical models: 1...
January 15, 2018: Journal of Neuroimmunology
Jelena Ciric, Katarina Lazic, Slobodan Kapor, Milka Perovic, Jelena Petrovic, Vesna Pesic, Selma Kanazir, Jasna Saponjic
In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0...
February 26, 2018: Behavioural Brain Research
Neal R Swerdlow, Savita G Bhakta, Jo A Talledo, Daniel M Franz, Erica L Hughes, Brinda K Rana, Gregory A Light
Prepulse inhibition (PPI) of startle is being explored both as an indicator of target engagement for, and a biomarker predicting the sensitivity to, procognitive effects of drugs. We now report the effects of the pro-attentional drug, d-amphetamine, on PPI and neurocognition in antipsychotic-medicated schizophrenia patients and healthy subjects (HS) who were also tested in a targeted cognitive training (TCT) module. 44 HS and 38 schizophrenia patients completed a double-blind, placebo-controlled crossover study of the effects of a single dose of amphetamine (10 mg po) on PPI and MATRICS Consensus Cognitive Battery (MCCB) performance; TCT results were previously reported from 60 of these subjects...
March 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ciaràn M Fitzpatrick, Vojislav S Maric, Simon T Bate, Jesper T Andreasen
Impulsivity is a characteristic of a number of neuropsychiatric disorders such as attention-deficit/hyperactivity disorder. The 5-choice serial reaction time task (5-CSRTT) is a rodent paradigm extensively used to assess attention and impulsivity. Notably, 5-CSRTT studies do not typically account for the reduction in premature responding, the measure of impulsive action, occurring upon repeated exposure to test sessions with long or variable intertrial intervals (ITIs). This present 5-CSRTT study investigated the use of variable ITIs (5, 10 or 15s) across 15 test days (4 training days followed by 1 drug test day per week for three weeks) as previous experience had shown that 4 training days would be sufficient to induce consistent premature response levels in male C57BL/6J mice...
November 2, 2017: Neuroscience Letters
Kenneth J Broadley, Harrison D Broadley
Sympathomimetic and trace amines, including β-phenylethylamine (PEA) and amphetamine, increase blood pressure and constrict isolated blood vessels. By convention this is regarded as a sympathomimetic response, however, recent studies suggest trace amine-associated receptor (TAAR) involvement. There is also uncertainty whether these amines also release nitric oxide (NO) causing opposing vasodilatation. These questions were addressed in guinea-pig isolated aorta, a species not previously examined. Guinea-pig aortic rings were set up to measure contractile tension...
January 5, 2018: European Journal of Pharmacology
Dustin J Stairs, Sarah E Ewin, Megan M Kangiser, Markus N Pfaff
Adolescent nicotine exposure has been shown to lead to further psychostimulant use in adulthood. Previous preclinical research in rats has shown that environmental enrichment may protect against drug abuse vulnerability. The current study was designed to examine whether environmental enrichment can block the ability of adolescent nicotine exposure to increase d-amphetamine self-administration in adulthood. Male Sprague-Dawley rats were raised in either enriched conditions (ECs) or isolated conditions (ICs) and then injected with saline or nicotine (0...
October 2017: Experimental and Clinical Psychopharmacology
Megan J Moerke, Matthew L Banks, Kejun Cheng, Kenner C Rice, S Stevens Negus
BACKGROUND: Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice...
December 1, 2017: Drug and Alcohol Dependence
David A MacQueen, Arpi Minassian, Brook L Henry, Mark A Geyer, Jared W Young, William Perry
OBJECTIVES: Amphetamine improves vigilance as assessed by continuous performance tests (CPT) in children and adults with attention deficit hyperactivity disorder (ADHD). Less is known, however, regarding amphetamine effects on vigilance in healthy adults. Thus, it remains unclear whether amphetamine produces general enhancement of vigilance or if these effects are constrained to the remediation of deficits in patients with ADHD. METHODS: We tested 69 healthy adults (35 female) on a standardized CPT (Conner's CPT-2) after receiving 10- or 20-mg d-amphetamine or placebo...
October 16, 2017: Journal of the International Neuropsychological Society: JINS
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