Effects of acute and chronic doses of naltrexone on ethanol self-administration in Rhesus monkeys

The effects of acute and chronic administration of intramuscular naltrexone (0.1, 0.3, 1.0, and 3.0 mg/kg) on oral ethanol (8%) self-administration were examined. Naltrexone (1.0 mg/kg) effects on the self-administration of ethanol concentrations ranging from 0.5 to 8% (w/v) were also investigated. Rhesus monkeys with substantial histories of drug and ethanol drinking served as subjects. During daily 3-hr sessions, monkeys were presented with ethanol solutions, concurrently available with water, under fixed-ratio reinforcement schedules. Naltrexone decreased the consumption of ethanol (g/kg). Biphasic temporal effects were observed within sessions. Naltrexone dose-dependently decreased the number of ethanol deliveries by a maximum of 56% (n = 18; 3 monkeys x 6 sessions) during the first hour of the session. During the second and third hours, however, ethanol intake recovered such that maximum decreases over the 3-hr session were similar to 27% (n = 18), and the mean decrease was 16% (n = 18). Often marked tolerance was observed, such that the effects of acute naltrexone administration were greater than effects after chronic administration. The self-administration of low ethanol concentrations (less than or equal to 2% w/v) was increased in several monkeys, by up to 340%, after naltrexone pretreatment. In summary, the effects of naltrexone on ethanol self-administration, in drug-and alcohol-experienced rhesus monkeys, are not characterized by unitary decreases in measures of ethanol self-administration. Rather, differential naltrexone effects were a function of experimental parameters, including the dose and number of naltrexone injections.