Ethanol-reinforced behaviour in the rat: effects of naltrexone

It has been repeatedly reported that endogenous opioid pathways play an important role in ethanol drinking behaviour. In line with these findings, a non-selective opioid receptor antagonist, naltrexone, seems to reduce relapse rates in detoxified alcoholics. The aim of the present study was to evaluate the effects of naltrexone on (i) ethanol self-administration; (ii) extinction of responding for ethanol; (iii) reinstatement of ethanol-seeking induced by non-contingent presentations of ethanol-associated stimuli. Male Wistar rats were trained to lever-press for 8% ethanol in an operant procedure where ethanol was introduced in the presence of sucrose. The selectivity of naltrexone's actions was assessed by studying its effects on water-reinforced behaviour in separate control experiments. Acute injections of naltrexone (1 or 3 mg/kg) did not alter ethanol self-administration. Repeated treatment with naltrexone (3 mg/kg, before three consecutive self-administration sessions) progressively reduced ethanol intake. In the extinction procedure, acute administration of 3 mg/kg naltrexone suppressed responding previously reinforced with ethanol. Similarly, naltrexone (1-3 mg/kg) potently and dose-dependently inhibited reinstatement of ethanol-seeking produced by non-contingent deliveries of the liquid dipper filled with 8% ethanol. In the control experiments, lower doses of naltrexone (1-3 mg/kg) did not exert any effect on either reinforced or non-reinforced (extinction) lever-pressing for water. These results indicate that: (i) subchronic treatment with naltrexone leads to progressive reduction of ethanol self-administration; (ii) single doses of naltrexone may increase extinction and attenuate cue-induced reinstatement of ethanol-reinforced behaviour.