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

Rationale: Drugs that reduce relapse in alcoholics are thought Co inhibit either positive reinforcement for drinking (e.g. naltrexone) or negative reinforcement (e.g. acamprosate), and may reduce the impact of conditioned stimuli associated with previous alcohol use. We have developed a model for such conditioning by repeatedly pairing ethanol administration with plus-maze exposure. Substitution of saline for ethanol greatly increased stretched-attend postures and time in the central square, conditioned to the environment. Objective: To test the hypothesis that if this behaviour indicates a negative affective state caused by the expectation of ethanol, it should be inhibited by drugs that reduce negative, but not positive, reinforcement. Methods: The effects of naltrexone and acamprosate on alcohol-conditioned abstinence behaviour were compared. Results: Acute administration of either drug alone produced no significant effects on plus-maze behaviour in naive mice. Naltrexone had no significant effect on the alcohol-conditioned abstinence behaviour, but acamprosate reduced the incidence of stretched-attend postures. Conclusions: The experiments replicated previous findings for alcohol/environment conditioned behaviour, and demonstrated, as predicted? that this was decreased by acamprosate but not by naltrexone. Effects of acamprosate on conditioned negative reinforcement may be the cause of this effect, but more work is required to establish the usefulness of this model in evaluation of anti-relapse drugs.