Central Amygdala Vasopressin Activity in Withdrawal-Related Affect from Chronic Adolescent Binge Episodes

PROJECT SUMMARY Withdrawal from alcohol exposure is associated with alcohol use disorder, but much remains unknown about withdrawal responses during adolescence in males and females. Our lab utilizes a chronic exposure paradigm of adolescent binge alcohol exposure that results in increased social anxiety (indexed via reduced social interaction in the modified social interaction test) in both sexes. However, a sex-specific increase in pro-stress neuropeptide vasopressin (AVP) is evident in males, but not females in the central amygdala (CeA), supporting that sex-dependent mechanisms may drive anxiogenic responses during withdrawal from alcohol. This proposal is designed to test the overarching hypothesis that social dysfunction during acute withdrawal from repeated binge episodes during adolescence alters the functional properties of sex-specific CeA neurons implicated in anxiety, with withdrawal-related activation of the AVP system within the CeA mediating these effects in male but not female rats. This hypothesis will be tested in Aim 1 by determining which GABAergic subtypes in the CeA are activated during social interaction following acute ethanol withdrawal, and if the GABAergic properties of activated neurons are changed by withdrawal. In Aim 2, we will assess the co-localization of AVP receptor (V1aR and V1bR) mRNA in CeA neuron subtypes activated during social interaction, and if bath application of AVP receptor antagonists changes the GABAergic properties of activated neurons. Behavioral analysis will then be done to test whether systemic AVP receptor antagonism reverses social behavior alterations following repeated adolescent binge episodes in both males and females. Collectively, these studies will assess CeA-specific neuronal mechanisms related to social behavior during withdrawal from chronic adolescent binge ethanol exposure and address the role of the AVP system. Training will incorporate multiple techniques, and the guidance of my mentorship team will provide me with crucial skills to broaden my conceptual and technical repertoire, along with necessary professional development to provide the framework towards attaining a postdoc position and pathway towards being an independent scientist.