Extended Amygdala Circuits, Neuropeptide and Neuroimmune Signaling, and Sex Differences in Alcohol Use Disorder

Alcohol use disorder (AUD) involves persistent changes in stress-responsive and motivational circuits, but the relationships among neuropeptide signaling, neuroimmune responses, and sex-dependent behavioral effects remain incompletely defined. This focused narrative review critically evaluates experimental evidence concerning neuropeptide Y (NPY) and its Y1 receptor (Y1R), corticotropin-releasing factor (CRF), and inflammatory signaling in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST), alongside selected glucagon-like peptide-1 receptor (GLP-1R) studies relevant to translation. Literature was identified through targeted database searches and reference tracking, with emphasis on causal manipulations, anatomical specificity, behavioral models, and clinical endpoints. The evidence supports distinct effects of manipulating CeA Y1R-expressing projections and activating Y1 receptors, and indicates that NPY can regulate inhibitory inputs to BNST CRF neurons. Inflammasome-related findings are region-, exposure-, and model-dependent; direct causal links to defined extended amygdala neuropeptide circuits remain to be established. Sex-specific findings require adequately powered interaction tests rather than comparisons of significance within each sex. GLP-1R studies provide therapeutic context but do not establish a common mechanism in the extended amygdala. Future experiments should distinguish parallel pathways from circuit convergence and molecular mediation using cell-specific perturbations, physiological readouts, and behavioral rescue.