The ethanol self-administration context as a reinstatement cue: acute effects of naltrexone

A major difficulty in treating alcohol addiction is the high rate of relapse even after prolonged abstinence. Relapse can be triggered by several factors, including stress, re-exposure to the drug, conditioned discrete stimuli and exposure to the context in which alcohol consumption occurred. The present study investigated the role played by the environmental context on ethanol relapse using an extinction/reinstatement animal model: rats were trained to self-administer ethanol in a distinctive context, and extinction occurred in a setting that differed by visual, tactile and olfactory properties; reinstatement was tested by placing the animals into the ethanol-associated context in the absence of ethanol. We found that re-exposure to the ethanol-associated context significantly increased responses on the ethanol-paired lever. The increase in responding required the presence of the complete configuration of the multimodal context. The non-selective opioid receptor antagonist naltrexone (0.3 mg/kg) administered 20 min prior to the reinstatement test significantly attenuated context-induced reinstatement of lever press responding, compared with saline-treated subjects. These data indicate that the environmental context associated with ethanol availability influences ethanol-seeking behavior in the rat, and that endogenous opioids are involved in this process. Our findings are in accordance with clinical reports demonstrating naltrexone efficacy in the treatment of alcohol relapse in humans, and indicate that the context-induced reinstatement model described here may be useful to investigate the biological mechanisms underlying alcohol relapse.