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Tuesday, June 17, 2008

Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala
PNAS | June 17, 2008 | vol. 105 | no. 24 | 8410-8415


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{varepsilon} exhibit reduced anxiety-like behavior and alcohol consumption, we investigated whether PKC{varepsilon} lies downstream of CRF1 receptors in the CeA.

Compared with PKC{varepsilon}+/+ CeA neurons, PKC{varepsilon}–/– neurons showed increased GABAergic tone due to enhanced GABA release. CRF and ethanol stimulated GABA release in the PKC{varepsilon}+/+ CeA, but not in the PKC{varepsilon}–/– CeA. A PKC{varepsilon}-specific inhibitor blocked both CRF- and ethanol-induced GABA release in the PKC{varepsilon}+/+ CeA, confirming findings in the PKC{varepsilon}–/– CeA.

These results identify a PKC{varepsilon} signaling pathway in the CeA that is activated by CRF1 receptor stimulation, mediates GABA release at nerve terminals, and regulates anxiety and alcohol consumption.

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Request Reprint E-Mail: mroberto@scripps.edu
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