Involvement of the opioid system in the development and expression of sensitization to the locomotor-activating effect of ethanol.

Previous studies have shown that pretreatment with naloxone (Nlx), an opiate antagonist, attenuates the stimulating effect of ethanol. The purpose of the present study was to determine the influence of Nlx on the development and expression of the sensitization to ethanol. Initially, effects of different doses of Nlx on the response to a low dose of ethanol (2.0 g/kg) were assessed. Nlx (1.0 and 3.0 mg/kg i.p.) decreased the stimulating effect of ethanol. Groups of mice were treated with saline or Nlx (1.0 mg/kg i.p.) plus saline or ethanol (2.0 g/kg i.p.) during 21 d. On day 25 of treatment all animals received an ethanol challenge (2.0 g/kg i.p.). It significantly increased the locomotor activity of mice that had received chronic ethanol (2.0 g/kg) once daily as compared to those that had received saline. Chronic administration of Nlx (1.0 mg/kg i.p.), during the same period of time, did not change the locomotor activity of the mice. However, the group concomitantly treated with Nlx+ethanol did not develop sensitization to the locomotor-activating effect of ethanol. Another experiment was carried out to determine the effects of Nlx on the expression of sensitization to ethanol. Acute pretreatment with Nlx did not change the response of the mice that had developed sensitization to ethanol. These data show Nlx's prevention of the development of ethanol-induced sensitization but not of its expression, suggesting an important role of the opioid neurotransmitter systems modulating the development of sensitization to the locomotor-activating effect of ethanol.