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Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.
- Source :
-
Drug and alcohol dependence [Drug Alcohol Depend] 2017 Dec 01; Vol. 181, pp. 85-93. Date of Electronic Publication: 2017 Oct 13. - Publication Year :
- 2017
-
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.<br />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.<br />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.<br />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.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Intravenous
Animals
Cocaine administration & dosage
Dose-Response Relationship, Drug
Drug Interactions
Food
Macaca mulatta
Male
Morphine pharmacology
Naltrexone analogs & derivatives
Receptors, Opioid, mu agonists
Receptors, Opioid, mu antagonists & inhibitors
Reinforcement, Psychology
Self Administration
Choice Behavior drug effects
Cocaine pharmacology
Dextroamphetamine pharmacology
Naltrexone pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0046
- Volume :
- 181
- Database :
- MEDLINE
- Journal :
- Drug and alcohol dependence
- Publication Type :
- Academic Journal
- Accession number :
- 29040826
- Full Text :
- https://doi.org/10.1016/j.drugalcdep.2017.09.020