Neurobiological Basis of Aversion-Resistant Ethanol Seeking in C. elegans

Persistent alcohol seeking despite the risk of aversive consequences is a crucial characteristic of alcohol use disorders (AUDs). Therefore, an improved understanding of the molecular basis of alcohol seeking despite aversive stimuli or punishment in animal models is an important strategy to understand the mechanism that underpins the pathology of AUDs. Aversion-resistant seeking (ARS) is characterized by disruption in control of alcohol use featured by an imbalance between the urge for alcohol and the mediation of aversive stimuli. We exploited C. elegans, a genetically tractable invertebrate, as a model to elucidate genetic components related to this behavior. We assessed the seb-3 neuropeptide system and its transcriptional regulation to progress aversion-resistant ethanol seeking at the system level. Our functional genomic approach preferentially selected molecular components thought to be involved in cholesterol metabolism, and an orthogonal test defined functional roles in ARS through behavioral elucidation. Our findings suggest that fmo-2 (flavin-containing monooxygenase-2) plays a role in the progression of aversion-resistant ethanol seeking in C. elegans.