Alcohol use disorders (AUDs) impart a huge financial (in excess of $250 billion) and societal strain. In order to develop pharmacological and behavioral therapies to treat AUDs, therefore, it is important to understand the neural circuitry and neuroadaptation that occurs in the transition to excessive consumption of alcohol use. The focus of this application is on a population of neurotensin (NTS) neurons the central nucleus of the amygdala (CeA). Utilizing genetic, cre-recombinase strategies in conjunction with selective lesioning (caspase3) and optogenetic (channel rhodopsin) strategies, we have found that these neurons, via their projections to the parabrachial nucleus (PBN), regulate both excessive consumption of alcohol, and reward-like behaviors. In this proposal we hypothesize that GABAergic signaling within the NTSCeA and in the NTSCeA?PBN mediates reward and ethanol consumption behaviors. We will explore this hypothesis over 3 converging aims.
Aim 1 will probe the role of signaling molecules within NTSCeA neurons on reward, alcohol consumption and appetitive behavior.
Aim 2 will further probe the role of GABAergic signaling within the NTSCeA?PBN projection. Finally, Aim 3 will explore physiological adaptation within these circuits. Together, these aims provide an innovative framework to discern how specific projections within the brain are influencing the reward behavior and consumption of alcohol.
Alcohol Use Disorders (AUDs) are medical conditions in which excessive consumption of alcohol is thought to promote transitions from moderate social drinking to the development of AUDs. It is therefore critical to understand which neuronal circuits and adaptations promote both early alcohol seeking and later excessive alcohol consumption. This application is using advanced technologies to probe specific neuronal pathways in the context of alcohol drinking.
