Background

Alcohol is a widely abused drug with a plethora of associated diseases that can impact societal functioning. Multiple studies have focused on unravelling the mode of action and effect of this drug; however, the neuronal mechanisms underlying alcohol susceptibility and disinhibition are unclear. Studies across various species have demonstrated that alcohol intake increases the release of the neurotransmitter DA that induces the reward pathway (Imperato and Di Chiara, 1986; Weiss et al., 1996; Baik, 2013). Although C. elegans does not mimic all the complexities of the mammalian system, it has been successfully modeled for studying alcohol-dependent neuronal behaviors. Studies show that C. elegans display diverse aspects of alcohol responses (Davies et al., 2003 and 2004). Previously, investigations in C. elegans have revealed that there is a dose-dependent decline in the locomotor activity upon acute and chronic alcohol exposure at a concentration of 400-500 mM (Davies et al., 2003; Lee et al., 2009). The DA system in C. elegans is involved in feeding, movement, learning, and memory; and similar to that of mammals, signals through two receptor subfamilies D1-like and D2-like receptors. Mutants of the D2-like receptor, dop-2, exhibited no obvious phenotype when analyzed for DA-dependent behaviors, despite being expressed in all dopaminergic neurons and predicted to be an autoreceptor (Chase et al., 2004). We devised an assay utilizing the EIS behavior observed in mutants of dop-2 to investigate the neuronal circuitry involved in regulating locomotory behavior under the influence of EtOH (Pandey et al., 2021).