EB Palmieri 1, B Bryd 1, L Sutton 1

Alcohol use disorder (AUD) affects 1 in 10 people in the United States alone, causing significantly reduced quality of life in affected individuals. Despite the prevalence and social, economic, and medical burdens associated with AUD, understanding of genetic contributors remains limited. One of the major molecular mechanisms underlying alcohol seeking and reward is mammalian target of rapamycin complex 1 (mTORC1) signaling. mTORC1 is the master cell growth regulator; it is ubiquitously expressed, and it integrates nutrient signals in order to direct cell growth through a general translation mechanism. In the brain mTORC1 is involved in neuronal growth, in part directing formation of learning and memory. Through this process, mTORC1 is thought to encode the rewarding effects of addictive stimuli. In fact, research has found that abnormal mTORC1 activity alters drug seeking, including ethanol seeking. However, the exact mechanism through which mTORC1 affects drug seeking is poorly understood. Here, we investigate the role of a novel modulator of mTORC1 signaling with specific neuronal expression, GPR155, on ethanol-related behavior. We investigated recovery from ethanol-induced sedation as well as ethanol drinking paradigms in a GPR155 knockout mouse model. While we find that motor recovery from ethanol-induced sedation and blood ethanol clearance are unaffected by GPR155 knockout status, ethanol preference is decreased in socially-housed female GPR155 knockout mice. Findings are not only the first to identify the behavioral role of GPR155, but they are also the first to identify its role in ethanol drinking behaviors, identifying it as a novel target of alcohol research.

1Biology Department University of Maryland Baltimore County, Baltimore, MD, USA