Adolescent Ethanol Exposure Reduces Central Amygdala GABA Transmission But Preserves Noradrenergic Signaling In Adulthood.

Abstract

Early initiation of alcohol use is a risk factor for developing alcohol use disorder (AUD) later in life, yet the long-term neuronal consequences of adolescent drinking remain poorly understood. The central amygdala (CeA) drives the negative emotional states that promote excessive drinking, and its overactivation is a hallmark of AUD in adults. Moreover, alcohol releases the stress signal norepinephrine (NE) into the adult CeA, leading to sex-dependent changes in its GABA transmission. Whether similar alcohol-induced changes in the adolescent CeA contribute to later-life vulnerability to AUD is unknown. In the present study, we used an intragastric gavage model of adolescent intermittent ethanol (AIE) exposure in Sprague-Dawley rats to examine the long-lasting effects on CeA synapses and noradrenergic regulation. AIE reduced basal GABA transmission via pre- and postsynaptic mechanisms in adults of both sexes, a response that deviates from the typical increased inhibition found in subjects only exposed to ethanol during adulthood. We observed similar NE-induced increases in CeA GABA release in adult males and females regardless of AIE exposure, and no differences were observed in CeA adrenergic receptor gene expression. Collectively, our data reveal that AIE produced a long-lasting reduction in adult CeA inhibitory tone, and this change is likely independent of the noradrenergic system. This developmental-specific shift in CeA activity reflects the heightened vulnerability of the adolescent brain to ethanol-induced neuroadaptation and may represent a neural substrate underlying the increased risk of AUD following adolescent alcohol use.