Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses

Version 1 : Received: 16 June 2022 / Approved: 16 June 2022 / Online: 16 June 2022 (08:41:35 CEST)

A peer-reviewed article of this Preprint also exists.

Rodriguez, L.; Kirson, D.; Wolfe, S.A.; Patel, R.R.; Varodayan, F.P.; Snyder, A.E.; Gandhi, P.J.; Khom, S.; Vlkolinsky, R.; Bajo, M.; Roberto, M. Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses. Int. J. Mol. Sci. 2022, 23, 7842. Rodriguez, L.; Kirson, D.; Wolfe, S.A.; Patel, R.R.; Varodayan, F.P.; Snyder, A.E.; Gandhi, P.J.; Khom, S.; Vlkolinsky, R.; Bajo, M.; Roberto, M. Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses. Int. J. Mol. Sci. 2022, 23, 7842.

Journal reference: Int. J. Mol. Sci. 2022, 23, 7842
DOI: 10.3390/ijms23147842

Abstract

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

Keywords

corticotropin releasing factor (CRF); patch-clamp electrophysiology; sex difference; alcohol use disorder (AUD); Gamma-Aminobutyric Acid (GABA); central amygdala (CeA); spontaneous inhibitory post synaptic currents (sIPSCs)

Subject

LIFE SCIENCES, Cell & Developmental Biology

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