Acute Ethanol Significantly Enhances GABAergic Transmission in the Central Lateral Amygdala of Alcohol-Naïve and Alcohol-Dependent Male Rats.

BACKGROUND

The central nucleus of the amygdala (CeA), a key component of the extended amygdala, is critical for mediating behavioral and physiological responses to stress and alcohol exposure. While extensive research has characterized alcohol's effects on GABAergic transmission in the medial CeA (CeM), the lateral CeA (CeL) remains underexplored, despite its central role in upstream signaling within the CeA circuit.

METHODS

In this study, we examined the effects of acute ethanol (EtOH) on GABAergic transmission in the CeL of alcohol-naïve and alcohol-dependent male and female Wistar rats. Alcohol dependence was induced using a chronic intermittent ethanol vapor exposure protocol. Whole-cell patch-clamp recordings were conducted on CeL neurons to measure spontaneous inhibitory postsynaptic currents (sIPSCs) at baseline and following acute application of 44 mM EtOH.

RESULTS

Acute EtOH significantly increased sIPSC frequency in CeL neurons from male rats, regardless of alcohol history, indicating enhanced presynaptic GABA release. In contrast, female rats showed no significant changes in sIPSC frequency or amplitude following acute EtOH application, whether alcohol-naïve or dependent. Several neuronal properties-including membrane resistance, holding current, and rheobase-were significantly altered in alcohol-dependent females. However, overall spiking characteristics and baseline inhibitory transmission did not differ significantly between naïve and dependent groups within each sex.

CONCLUSIONS

These findings reveal, for the first time, that acute EtOH produces sex-specific effects on GABAergic transmission in the CeL, enhancing inhibitory signaling in males but not females. This pattern mirrors previous observations in the CeM and underscores the importance of including both sexes in alcohol research. Understanding the mechanisms underlying these differences may inform the development of sex-specific treatments for alcohol use disorder.