Original Publication Date
Drug and Alcohol Dependence
DOI of Original Publication
Date of Submission
Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys.
Behavior was maintained under a concurrent schedule of food delivery (1 g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0–0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n = 3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0–10 mg/kg/day, intramuscular) treatment periods.
Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2–10 mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets.
Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction.
© 2016 The Author(s). Published by Elsevier Ireland Ltd
Is Part Of
VCU Pharmacology and Toxicology Publications