Sex Differences in the Alcohol-Mediated Modulation of BLA Network States

Alcohol use, reported by 85% of adults in the United States, is highly comorbid with mood disorders, like generalized anxiety disorder and major depression. The basolateral amygdala (BLA) is an area of the brain that is heavily implicated in both mood disorders and alcohol use disorder. Importantly, the modulation of BLA network/oscillatory states via parvalbumin (PV)-positive GABAergic interneurons has been shown to control the behavioral expression of fear and anxiety. Further, PV interneurons express a high density of δ subunit-containing GABA(A) receptors (GABA(A)Rs), which are sensitive to low concentrations of alcohol. Therefore, we hypothesized that the effects of alcohol may modulate BLA network states that have been associated with fear and anxiety behaviors via δ-GABA(A)Rs on PV interneurons in the BLA. Given the impact of ovarian hormones on the expression of δ-GABA(A)Rs, we also examined the ability of alcohol to modulate local field potentials in the BLA from male and female C57BL/6J and Gabrd(−/−) mice after acute and repeated exposure to alcohol. Here, we demonstrate that acute and repeated alcohol can differentially modulate oscillatory states in male and female C57BL/6J mice, a process that involves δ-GABA(A)Rs. This is the first study to demonstrate that alcohol is capable of altering network states implicated in both anxiety and alcohol use disorders.