Acamprosate, but not naltrexone, inhibits conditioned abstinence behaviourassociated with repeated ethanol administration and exposure to a plus-maze

Rationale: Drugs that reduce relapse in alcoholics are thought Co inhibit e ither positive reinforcement for drinking (e.g. naltrexone) or negative rei nforcement (e.g. acamprosate), and may reduce the impact of conditioned sti muli associated with previous alcohol use. We have developed a model for su ch conditioning by repeatedly pairing ethanol administration with plus-maze exposure. Substitution of saline for ethanol greatly increased stretched-a ttend postures and time in the central square, conditioned to the environme nt. Objective: To test the hypothesis that if this behaviour indicates a ne gative affective state caused by the expectation of ethanol, it should be i nhibited by drugs that reduce negative, but not positive, reinforcement. Me thods: The effects of naltrexone and acamprosate on alcohol-conditioned abs tinence behaviour were compared. Results: Acute administration of either dr ug alone produced no significant effects on plus-maze behaviour in naive mi ce. Naltrexone had no significant effect on the alcohol-conditioned abstine nce behaviour, but acamprosate reduced the incidence of stretched-attend po stures. Conclusions: The experiments replicated previous findings for alcoh ol/environment conditioned behaviour, and demonstrated, as predicted? that this was decreased by acamprosate but not by naltrexone. Effects of acampro sate on conditioned negative reinforcement may be the cause of this effect, but more work is required to establish the usefulness of this model in eva luation of anti-relapse drugs.