Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys

Background: Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined. Methods: Continuous 21-day treatments with ramping doses of d-amphetamine (days 1-7: 0.032 mg/kg/h; days 8-21: 0.1 mg/kg/h, i.v.) or risperidone (days 1-7: 0.001 mg/kg/h; days 8-14: 0.0032 mg/kg/h; days 15-21: 0.0056 mg/kg/h, i.v.) were administered to rhesus monkeys (n=4) with daily access to two types of cocaine self-administration sessions: (1) a 2-h 'choice' session with concurrent availability of 1-g food pellets and intravenous cocaine injections (0-0.1 mg/kg per injection) and (2) a 20-h 'extended-access' session with 0.1 mg/kg per injection cocaine availability. Results: Total daily cocaine intake increased >6-fold during extended cocaine access. d-Amphetamine significantly decreased total cocaine intake, but not cocaine vs food choice. In contrast, risperidone did not significantly alter either total cocaine intake or cocaine vs. food choice. Conclusions: These results confirm and extend previous results supporting treatment effectiveness for monoamine releasers, but not dopamine antagonists, to reduce cocaine self-administration. Moreover, these results suggest amphetamine treatment efficacy to decrease preclinical cocaine vs. food choice may depend upon cocaine access conditions. (C) 2016 Elsevier Ireland Ltd. All rights reserved.