Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala

In the central amygdala (CeA), ethanol acts via corticotrophin-releasing factor (CRF) type 1 receptors to enhance GABA release. Amygdala CRF mediates anxiety associated with stress and drug dependence, and it regulates ethanol intake. Because mutant mice that lack PKC epsilon exhibit reduced anxiety-like behavior and alcohol consumption, we investigated whether PKC epsilon lies downstream of CRF1 receptors in the CeA. Compared with PKC epsilon(+/+) CeA neurons, PKC epsilon(-/-) neurons showed increased GABAergic tone due to enhanced GABA release. CRF and ethanol stimulated GABA release in the PKC epsilon(+/+) CeA, but not in the PKC epsilon(-/-) CeA. A PKCE-specific inhibitor blocked both CRF- and ethanol-induced GABA release in the PKC epsilon(+/+) CeA, confirming findings in the PKC epsilon(-/-) CeA. These results identify a PKCE signaling pathway in the CeA that is activated by CRF1 receptor stimulation, mediates GABA release at nerve terminals, and regulates anxiety and alcohol consumption.