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 × 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 ∼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 (≤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, the ethanol concentration, and the time point of measurement.