title: Influence of aripiprazole pretreatment on the reinforcing effects of methamphetamine in humans.
abstract: Methamphetamine use disorders remain a significant public health concern. Methamphetamine produces its behavioral effects by facilitating release of monoamines like dopamine (DA) and serotonin (5-HT). Results from animal studies show that acute pretreatment with DA and 5-HT antagonists attenuates the effects of methamphetamine, but this area remains largely unexplored in humans. This study sought to assess whether aripiprazole, a partial agonist at D2/5-HT1A receptors and an antagonist at 5-HT2A receptors, would attenuate the reinforcing and subject-rated effects of oral methamphetamine. Seven subjects with histories of recreational stimulant use completed a placebo-controlled, crossover, double-blind protocol in which they first sampled doses of oral methamphetamine (0, 4, 8 or 16 mg) following acute pretreatment with aripiprazole (0 and 15 mg). During each Sampling Session, subjects also completed a battery of subject-rated, cardiovascular, and other performance measures. In subsequent Self-Administration Sessions, subjects were provided the opportunity to earn the previously sampled methamphetamine dose on a progressive-ratio procedure. Methamphetamine functioned as a reinforcer, and produced prototypical stimulant-like subject-rated and cardiovascular effects (e.g., increased ratings of Stimulated; elevated blood pressure). Aripiprazole reduced methamphetamine self-administration and attenuated some of the positive subject-rated effects of methamphetamine (e.g., ratings of Like Drug). These results indicate that acute aripiprazole pretreatment attenuates the abuse-related effects of methamphetamine.
authors.affiliation: University of Kentucky College of Medicine, Department of Behavioral Science, 140 Medical Behavioral Science Building, Lexington, KY 40536-0086, United States; University of Kentucky College of Arts and Sciences, Department of Psychology, 110 Kastle Hall, Lexington, KY 40506-0044, United States. Electronic address: william.stoops@uky.edu.
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.forename: J Adam
authors.initials: JA
authors.lastname: Bennett
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: Rajkumar J
authors.initials: RJ
authors.lastname: Sevak
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rush
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D000068180:Aripiprazole; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage*; D015363:Quinolones / Q000008:administration & dosage*; D012054:Reinforcement, Psychology; D012646:Self Administration; D019966:Substance-Related Disorders / Q000209:etiology* / Q000517:prevention & control*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D010879:Piperazines; D015363:Quinolones; D008694:Methamphetamine; D000068180:Aripiprazole
keywords: 3,4-methylenedioxymethamphetamine (ecstasy); 5-HT; ANOVA; Aripiprazole; DA; DSM-IV; DSST; Diagnostic and Statistical Manual of Mental Disorders IV; Humans; LHBP; Laboratory of Human Behavioral Pharmacology; MDMA; Methamphetamine; Monoamines; NSDUH; National Survey on Drug Use and Health; SAMHSA; SEM; Substance Abuse and Mental Health Services Administration; THC; analysis of variance; digit symbol substitution task; dopamine; hours; hr; kg; kilograms; methamphetamine HCL; methamphetamine hydrochloride; mg; milligrams; min; minute; serotonin; standard error of the mean; tetrahydrocannabinol