Open bar assay: A novel operant paradigm for examining motivated response and substance abuse in Drosophila melanogaster

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PROJECT SUMMARY/ ABSTRACT Individual variation in alcohol preference and self-administration facilitates compulsive alcohol seeking behavior. However, the circuit identity and function underlying individual variability in alcohol self-administration behaviors is still not well understood. The goal of this proposal is to identify subtle behavioral features, fundamental circuitry principles and neurophysiological dynamics underlying alcohol preference in the tractable model system Drosophila melanogaster. Aim 1 will employ a computer vision and machine learning approach to identify subtle behaviors that relate to alcohol preference and alcohol avoidance. In this Aim I hypothesize that animals that express alcohol preference display enhanced seeking behavior, in particular in response to alcohol self- administration whereas lower alcohol preference will manifest through avoidance and reduced locomotion. Aim 2 will employ thermogenetic inactivation, using the GAL4/UAS system, of learning and memory brain circuits we believe play a direct role in encoding alcohol preference. In this Aim I hypothesize that inactivation of our identified learning and memory brain circuits will directly suppress the expression of alcohol preference in flies. Aim 3 will investigate how the neurophysiological dynamics of our identified circuit differs between alcohol preferers and abstainers. I hypothesize that, in my identified circuit, alcohol exposure will result in robust neurophysiological responses in alcohol-preferers and that we will observe the opposite in alcohol abstainers. This work will provide a framework for predicting general circuit principles for escalation of alcohol self- administration in more complex brains, which is in alignment with NIAAA’s mission to support behavioral research on the causes of alcoholism and alcohol-related problems.