INVOLVEMENT OF ZONA INCERTA DOPAMINERGIC NEURONS IN COMPULSIVE ALCOHOL USE

The zona incerta (ZI), a subthalamic structure that remained poorly studied for a long time, is now recognized for its role in functions as varied as the regulation of attention, sleep, anxiety and motivated behaviors. In particular, the ZI is increasingly being studied for its involvement in eating and foraging behavior regulation. The ZI is a heterogeneous structure composed mainly of GABAergic neurons. But it also contains dopaminergic (DA) neurons, which have only recently been studied, and appear to be involved in these food-motivated behaviors. DA systems have been widely highlighted in research on addiction-related behaviors, particularly in their compulsive dimension. Compulsivity, defined as the repetition of actions despite negative consequences, appears central to the transition to addiction. Given the ZI's role in modulating various neurobiological functions, it could play a role in regulating the compulsive behaviors characteristic of addiction, via its interaction with the reward and motivation systems. However, its influence on these processes remains largely unexplored, as does the role of its DA neurons. We therefore propose to examine the involvement of ZI DA neurons in compulsive behaviors associated with alcohol addiction, using the rat animal model. We studied the effect of compulsive alcohol consumption on the activity of ZI DA neurons, using patch-clamp electrophysiology. We will then investigate whether a chemogenetic modulation of this activity can in turn influence the compulsivity of the animals. This approach will provide a better understanding of how this neuronal population may contribute to compulsivity, and potentially to the transition to addiction.