Naltrexone effects on food- and codeine-maintained responding in rhesus monkeys

Abstract

The delivery of food or the i.v. injection of codeine maintained lever pressing in rhesus monkeys during alternating periods of daily experimental sessions. Responding was maintained by food or codeine under a chain differential reinforcement of other behavior 30 sec (DRO 30), fixed-ratio 30 response (FR 30) schedule of reinforcement. Maximum FR rates of codeine-reinforced responding were maintained by 25–47 μg/kg per injection codeine. Both lower (8 μg/kg per injection) and higher (80–800 μg/kg per injection) doses of codeine maintained lower FR response rates. FR rates of food-maintained responding only decreased as a function of codeine dose. Response rates during the DRO component of the schedule, when either food or codeine maintained responding, were extremely low (<0.01 responses/sec) and these rates were generally unaffected by the codeine dose. Naltrexone (0.003–0.32 mg/kg i.m.), administered before experimental sessions, produced a dose-related shift to the right in the rate-decreasing effects of codeine on FR responding maintained by food. In contrast, the dose-effect curve relating the FR rate of codeine-maintained responding to codeine dose was shifted consistently to the right only by the lowest dose of naltrexone (0.003 mg/kg). Although a 10-fold higher dose of naltrexone, 0.03 mg/kg, initially shifted the codeine self-injection curve to the right in one monkey, these higher naltrexone doses (0.03–0.32 mg/kg) generally resulted in response rates as low as or lower than those maintained by saline,e across a wide range of codeine doses (25–800 μg/kg per injection). These data suggest that naltrexone may decrease codeine-reinforced responding by mechanisms other than, or in addition to, a competitive antagonism of codeine's reinforcing effects.