Cue-Reactivity and Alcohol Self-Dosing

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APPLICANT'S ABSTRACT: The goal of the proposed research is to develop a model of 'cue-reactivity' using a combination of classical conditioning and operant conditioning procedures. Environmental stimuli that have been repeatedly associated with drug and alcohol use elicit physiological and subjective drug-related effects in humans that abuse drugs and alcohol. Reactivity to drug-related stimuli (i.e., cues) is believed to be a function of classical conditioning processes and may play an important role in the development of compulsive alcohol drinking and in the propensity to relapse after periods of abstinence. A new animal model of cue reactivity has been under development in our laboratory in which a constellation of behaviors are reliably increased during presentation of a sequence of environmental stimuli (e.g., lights and tones) that precede the opportunity to consume alcohol, food or a preferred non-alcoholic beverage. These cue-related behaviors include time sensitive patterns of learned instrumental responses and general activity, as well as naturalistic behaviors. The proposed experiments will systematically examine the relationship between reactivity to alcohol-related cues, alcohol-seeking and self- administration. The first series of studies will evaluate whether cue-related behaviors are sensitive to the changes in the magnitude of the reinforcer (i.e., alcohol concentration) and amount of work effort required (i.e., number of lever responses) to obtain alcohol. These studies will also determine if there are differences in the type of behaviors that emerge with repeated drug-cue pairings and across a range of alcohol concentrations and response 'costs'. A second series of studies will evaluate the influence of length of abstinence on alcohol self- administration and reactivity to alcohol-related cues. A third series of studies will evaluate the interactions between environmental alcohol-related cues and the internal cues produced by alcohol itself on the reinstatement and maintenance of self-administration and cue-related behaviors. Acute 'priming' doses of alcohol or environmental cues will be presented under conditions in which alcohol is available for self-administration or withheld (i.e., abstinence). This research will determine whether cue-related behaviors reliably predict alcohol self-administration and reinstatement of drug-taking (i.e., relapse) during abstinence. This research will additionally provide important information on the behavioral processes underlying conditioned responses to drug-related cues in animals which may be relevant to cue-reactivity and drug-taking in humans.