Effects of chronic administration of dopamine D2‐like receptor agonists aripiprazole and (−)‐N‐propyl‐norapomorphine on food/cocaine choice in socially housed monkeys

Abstract

Dopamine D2‐like receptor partial agonists have been suggested as treatments for substance abuse. The goal of this study was to characterize the effects of D2‐like receptor agonists on the relative reinforcing strength of cocaine using a food‐drug choice procedure in socially housed cynomolgus monkeys. In daily self‐administration sessions, monkeys chose between food pellets and cocaine injections (0.003–0.1 mg/kg). The available cocaine dose increased during the session to generate a full dose‐effect curve each day. The high‐efficacy agonist (−)‐N‐propyl‐norapomorphine [(−)‐NPA; 0.001–0.0056 mg/kg] or the lower‐efficacy agonist aripiprazole (ARI; 0.01–0.1 mg/kg) was administered for 5 days; self‐administration was examined on Day 1 and Day 5. At least one ARI dose decreased cocaine choice in most dominant monkeys, but did not affect or increased cocaine choice in subordinates. In contrast, (−)NPA was more effective in decreasing cocaine choice in subordinate monkeys, although increases in cocaine choice were observed in most monkeys. Tolerance was rarely observed across days; in general effects of both drugs were maintained or exacerbated over 5 days. Results suggest that ARI and (−)‐NPA produce qualitatively different effects on the reinforcing strength of cocaine, perhaps due to differing intrinsic efficacies, and that the effects are modulated by social rank. Support: DA12460, DA10584.