View Program - 63rd Annual Drosophila Research Conference

Alcohol research has largely been focused on understanding the neural mechanisms underlying excessive or compulsive alcohol intake. However, humans display a wide-variety of drinking behaviors with some escalating alcohol consumption over time while others moderately drink or even abstain.Investigating the circuits and neural dynamics underlying this individual variation is critical for developing more effective treatments for alcohol use and abuse disorders. In Drosophila melanogaster, the neural circuits required for encoding valence include identifiable connections, genetic and/or biochemical profiles and characterized temporal changes underlying learning, making flies an ideal model for investigating escalation of ethanol self-administration. We developed a 3-day operant paradigm to evaluate the spectrum of behaviors associated with self-administration of a pharmacologically relevant dose of volatilized ethanol and compared these responses to an ethologically relevant ethanol odor. Similar to mammals, individual variation in self-administration behavior for a pharmacologically relevant dose of ethanol occurs with consecutive training sessions. Approximately 35% of flies escalate self-administration whereas 61% of flies remain stable and 4% of flies decrease self-administration. This contrasts significantly with self-administration of ethologically relevant ethanol odor where 8% flies escalate self-administration. Thermogenetically inactivating a simple two neuron cholinergic and dopaminergic mushroom body circuit altered population ethanol preference to decrease and increase ethanol self-administration, respectively. Our data provides the behavioral and neuroanatomical groundwork to subsequently investigate variability in physiology of identified circuits contributing to alcohol use disorder.

The circuit basis of operant self-administration for ethanol in Drosophila Melanogaster