Effect of naltrexone on acute tolerance to ethanol in UChB rats

The effect of naltrexone (a non-selective opioid receptor antagonist) on both alcohol consumption in a voluntary selection situation and acute tolerance to the motor impairment effect of ethanol was examined in female high alcohol-drinking (UChB) rats using the tilting plane test. In experiment 1, the effect of naltrexone on alcohol consumption was studied in UChB rats which were given a daily 1-h period access to a 10% (v/v) ethanol solution with food and water always available. Naltrexone in doses of 5 or 10 mg/kg intaperitoneal (i.p.) caused dose-dependent reduction in voluntary alcohol intake by 45% and 66%, respectively, without altering daily water intake. In experiment 2, the effect of naltrexone (5 mg/kg i.p.) on acute tolerance to motor impairment effect of a dose of 2.3 g ethanol/kg i.p. was examined. A comparison of control (C) and naltrexone (Nal) UChB groups indicated that naltrexone slowed the recovery of the motor activity and reduce acute tolerance development at comparable ethanol levels in cerebral blood. These results suggest a contribution of the opioid system to acute tolerance to ethanol.