Failure of naloxone to affect initial and acquired tolerance to ethanol in rats

The effects of naloxone on the initial sensitivity to ethanol and the subsequent changes in tolerance induced by prior ethanol treatment were studied in rats by using the drinking test for assessing behavioral effects. Naloxone (N) was administered concurrently with ethanol (E) in either 5 successive single doses spaced at 2-day intervals (Experiment 1) or during 4 days of chronic i.v. infusion (E: 9 g/kg, N: 9 mg/kg in 6 injections per day, Experiment 2). Both treatments produced an increase in nervous tolerance toward ethanol. However naloxone was found to exert no effect on either initial or acquired tolerance toward ethanol. The results are discussed in terms of possible relations between the CNS mechanisms involved in tolerance to morphine and ethanol.