University of North Carolina at Chapel Hill Graduate School
Doi
Abstract
Alcohol use disorder is characterized by maladaptive patterns of alcohol consumption, with emerging evidence suggesting that neuropeptide Y (NPY) signaling through Y1 and Y2 receptors (Y1R and Y2R) within the central amygdala (CeA) plays a critical role in modulating ethanol intake. This dissertation investigates the neural mechanisms underlying binge-like ethanol drinking, focusing on the involvement of Y1R+ CeA to lateral hypothalamus (LH) projections, dynamic interactions between Y1R and Y2R within the CeA, and the impact of chronic ethanol exposure on Y1R protein expression. Chapter 1 demonstrates that chemogenetic inhibition of Y1R+ CeA-LH projections selectively reduced binge-like ethanol drinking in male mice without affecting female mice. Chapter 2 expands on these findings by examining the dynamic interactions between Y1R and Y2R expression in the CeA and their relationship to ethanol intake. Administration of a transient intra-CeA Y1R agonist failed to influence ethanol consumption in either sex. However, chronic NPY overexpression via a viral vector revealed behavioral effects and predictive relationships between receptor mRNA expression and intake patterns. Chapter 3 investigates how a history of extended binge drinking influences Y1R protein expression in the CeA. Although no significant differences were found in Y1R/NeuN colocalization across sex and treatment groups, correlational analyses revealed that Y1R expression varied with individual ethanol consumption. Additionally, Y1R+ tracing data identified a subset of Y1R+ neurons projecting to the LH, potentially contributing to the modulation of binge-like ethanol intake, consistent with findings from Chapter 1. Collectively, these results support a model wherein Y1R signaling within the CeA regulates ethanol consumption through circuit-specific mechanisms and broader neuroadaptive changes influenced by sex and individual drinking patterns. This research advances our understanding of the neurobiological mechanisms underlying binge-like ethanol intake and highlights the complex, sex-dependent roles of NPY-Y1R and Y2R signaling in the CeA.Doctor of Philosoph
