1. Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.
- Author
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Moerke, Megan J., Banks, Matthew L., Cheng, Kejun, Rice, Kenner C., and Negus, S. Stevens
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AMPHETAMINE abuse , *NALTREXONE , *COCAINE abuse , *OPIOID receptors , *SUBSTANCE-induced disorders , *LABORATORY monkeys , *THERAPEUTICS , *ANIMAL experimentation , *CELL receptors , *COCAINE , *DECISION making , *DRUG interactions , *DOSE-effect relationship in pharmacology , *FOOD , *INTRAVENOUS therapy , *MORPHINE , *PRIMATES , *REINFORCEMENT (Psychology) , *RESEARCH funding , *SELF medication , *DEXTROAMPHETAMINE , *PHARMACODYNAMICS - Abstract
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.Methods: Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0-0.1mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs.Results: During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032-0.32mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice.Conclusions: These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption. [ABSTRACT FROM AUTHOR]- Published
- 2017
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