Reducing alcohol-seeking behavior in a rat model of alcohol dependence

PROJECT SUMMARY/ABSTRACT Excessive alcohol use is driven by various factors that are biological, psychological, and social in nature. The degree of how these factors contribute to problematic drinking and then relapse after recovery vary widely at the individual level. One common factor presented to all the users of alcohol is the set of cues closely linked to alcohol consumption. Environmental cues that reliably precede alcohol availability and subsequent consumption can gain the ability to elicit conditioned responses such as alcohol-seeking behavior and promote problematic drinking. Current treatment for alcohol use disorder includes cue-exposure therapy, a behavioral procedure in which alcohol cues are systematically presented in the absence of alcohol to promote a reduction or “extinction” of cue-conditioned responses. Unfortunately, extinction is rarely permanent: extinguished cue-conditioned alcohol-seeking responses are highly susceptible to relapse. We recently showed that a modification to standard extinction procedure (i.e., cue-induced memory retrieval session prior to extinction) blocked the return of alcohol- seeking behavior of rats with moderate level of alcohol consumption (Cofresi et al., 2017). This “retrieval+extinction” approach has enormous potential in that a simple modification to cue-exposure therapy protocols used in alcohol rehabilitation could significantly improve the odds of preventing relapse following treatment. It is thus crucial to extend our initial finding to a rat model of alcohol dependence that better mimics the human conditions of alcohol abuse. In fact, no study has systematically examined the nature and mechanism of extinction, let alone retrieval+extinction, in a rat model of alcohol dependence. Therefore, we will determine parameters that influence extinction and relapse of alcohol-seeking behavior in dependent rats, and further examine whether retrieval+extinction is equally effective at preventing relapse in dependent rats as it was in non- dependent rats. Then, we will probe the neural substrates underlying extinction of alcohol-seeking behavior in dependent rats and test the hypothesis that retrieval+extinction engages neural mechanisms that are distinct from standard extinction.