Abstract Pleasure or rewarding experiences serves as an adaptive process and are essential for healthy psychological functioning. The ability to experience pleasure is attributed to an individual’s hedonic tone or the ‘liking’ of a reward. Pathologically, low hedonic tone or anhedonia is the ability to experience pleasure, a key feature in depression. Hedonic tone can be measured by the palatability towards food or liquids. Recently, GPR162 has been implicated in hedonic food intake suggesting that this receptor contributes to reward-related behaviors by setting hedonic tone. GPR162 is an orphan G protein coupled receptor (GPCR) as its endogenous ligand is unknown and is an IDG eligible gene. The goal of this proposal is to identify the role of GPR162 towards hedonic tone by measuring palatability using a natural reward (sucrose) and to further examine its contribution to other aspects of reward including motivation and reinforcement. This project will use a viral mediated gene transfer approach to either knockdown or overexpress GPR162 in the nucleus accumbens, a region known to mediate reward-related behaviors. Finally, we will begin to address the signaling capabilities of GPR162. Our initial in vitro findings show GPR162 activates the RhoA pathway. Here we will move this line of research into our mouse models to gain a better understanding of GPR162 signaling. The results of this study will “illuminate” an understudied protein by identifying the specific role of GPR162 in reward-related behaviors and by generating reagents and data for the scientific community.

Abstract Narrative Brain-enriched orphan G protein coupled receptors (GPCRs) represent an untapped resource for therapeutic targets but their physiological and behavioral importance is unknown. The experiments proposed will demonstrate the behavioral role of GPR162 towards reward-related behaviors and provide a basic understanding of GPR162 contribution to normal brain function.