Sex Differences in Acute Alcohol Sensitivity of Naïve and Alcohol Dependent Central Amygdala GABA Synapses. (29th April 2021)

• Record Type: Journal Article
• Authors: Kirson, Dean; Khom, Sophia; Rodriguez, Larry; Wolfe, Sarah A; Varodayan, Florence P; Gandhi, Pauravi J; Patel, Reesha R; Vlkolinsky, Roman; Bajo, Michal; Roberto, Marisa
• Is Part Of: Alcohol and alcoholism. Volume 56:Number 5(2021)
• Page Start: 581
• Page End: 588
• Publication Date: 2021-04-29
• Subjects: Alcoholism -- Periodicals; 616.861005
• DOI: 10.1093/alcalc/agab034
• Languages: English
• ISSNs: 0735-0414

Abstract

Abstract: Aims: Alcohol use disorder (AUD) is linked to hyperactivity of brain stress systems, leading to withdrawal states which drive relapse. AUD differs among the sexes, as men are more likely to have AUD than women, but women progress from casual use to binge and heavy alcohol use more quickly and are more likely to relapse into repetitive episodes of heavy drinking. In alcohol dependence animal models of AUD, the central amygdala (CeA) functions as a hub of stress and anxiety processing and gamma-Aminobutyric acid (GABA)ergic signaling within the CeA is involved in dependence-induced increases in alcohol consumption. We have shown dysregulation of CeA GABAergic synaptic signaling in alcohol dependence animal models, but previous studies have exclusively used males. Methods: Here, we used whole-cell patch clamp electrophysiology to examine basal CeA GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) and the effects of acute alcohol in both naïve and alcohol dependent rats of both sexes. Results: We found that sIPSC kinetics differ between females and males, as well as between naïve and alcohol-dependent animals, with naïve females having the fastest current kinetics. Additionally, we find differences in baseline current kinetics across estrous cycle stages. In contrast to the increase in sIPSC frequency routinely found in males, acute alcohol (11–88 mM) had no effect on sIPSCs in naïve females, however the highest concentration of alcohol increased sIPSC frequency in dependent females. Conclusion: These results provide important insight into sex differences in CeA neuronal function and dysregulation with alcohol dependence and highlight the need for sex-specific considerations in the development of effective AUD treatment. Abstract : Short Summary: Female central amygdala (CeA) GABAA receptor current kinetics are faster than males and depend on estrous cycle, with alcohol dependent animals having slower kinetics. Acute alcohol increases presynaptic GABA release in male CeA but has no effect in naïve female CeA. High concentrations of alcohol increase GABA release in dependent female CeA.