Understanding the role of DOP 2 a dopamine autoreceptor in ethanol dependent locomotion of Caenorhabditis elegans

Abstract

Animals tend to respond to a variety of external stimuli by generating appropriate behavioral responses brought about by the modulation of their neuronal circuitry. Our study uses alcohol (ethanol), one of today s most widely abused drug. Although a lot of studies have focused on unravelling the mode of action to allow for addiction to alcohol, not much is known about how it functions to modulate behaviors such as locomotion. In my thesis, I have focused on understanding the neuronal circuitry that could play a role in regulating locomotory behavior under the influence of ethanol. This study uses the model organism C. elegans. Previous work using C. elegans shows that this organism can be modelled for studying important aspects of ethanol abuse, such as dose dependent decline in locomotor activity upon acute exposure to alcohol similar to the depressive effect of ethanol in other animal systems. Ethanol has been shown to mediate its action through diverse pathways, one of which is the dopaminergic pathway. The dopamine (DA) system in C. elegans is involved in the animals feeding, movement and learning and memory and functions through two types of receptor subfamilies D1-like and D2-like receptors. DOP-2, a D2-like family autoreceptor was found to have minimal role if any when studied for DA dependent behaviors and the functions of this receptor are still largely unknown. My work elaborates on how dopaminergic autoreceptor, DOP-2, regulates locomotion in the presence of ethanol. This study provides important insights into DOP-2 function, as it is difficult to assign specific roles to neuromodulators such as DOP-2, as they have roles in wide arrays of behaviors that can be very transient and subtle. In this study, we have used an ethanol (EtOH) based assay to screen the dopaminergic (DAergic) pathway mutants. We found that the DOP-2 autoreceptor mutant showed an ethanol induced sedative behavior (EIS), the animal moves in circles with decrease in body bends and amplitude. This behavior is DOP-2 dependent as we were