Dataset Information

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

ABSTRACT: 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 PKCepsilon exhibit reduced anxiety-like behavior and alcohol consumption, we investigated whether PKCepsilon lies downstream of CRF(1) receptors in the CeA. Compared with PKCepsilon(+/+) CeA neurons, PKCepsilon(-/-) neurons showed increased GABAergic tone due to enhanced GABA release. CRF and ethanol stimulated GABA release in the PKCepsilon(+/+) CeA, but not in the PKCepsilon(-/-) CeA. A PKCepsilon-specific inhibitor blocked both CRF- and ethanol-induced GABA release in the PKCepsilon(+/+) CeA, confirming findings in the PKCepsilon(-/-) CeA. These results identify a PKCepsilon signaling pathway in the CeA that is activated by CRF(1) receptor stimulation, mediates GABA release at nerve terminals, and regulates anxiety and alcohol consumption.

SUBMITTER: Bajo M

PROVIDER: S-EPMC2448850 | biostudies-other | 2008 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Bajo Michal M Cruz Maureen T MT Siggins George R GR Messing Robert R Roberto Marisa M

Proceedings of the National Academy of Sciences of the United States of America 20080609 24

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 PKCepsilon exhibit reduced anxiety-like behavior and alcohol consumption, we investigated whether PKCepsilon lies downstream of CRF(1) receptors in the CeA. Compared with PKCepsilon(+/+) CeA neurons, PKCepsilon(-/-) neurons showed incr ...[more]

PMID: 18541912

Similar Datasets

Project description:Withdrawal anxiety following chronic ethanol exposure is often associated with relapse in recovering alcoholics. It is likely that brain regions regulating anxiety-like behaviors adapt during chronic ethanol exposure to ultimately regulate such behaviors. The central amygdala contains numerous neurotransmitter systems that have been implicated in the regulation of anxiety-like behavior, including corticotropin releasing factor (CRF) and NMDA-type glutamate receptors. Chronic ethanol exposure causes functional adaptations in both CRF and NMDA receptors that are likely to regulate anxiety-like behaviors expressed during withdrawal. However, the molecular mechanisms governing these adaptations remain unexplored. We therefore evaluated these neurotransmitter systems in Sprague-Dawley rats during chronic ingestion of an ethanol-containing liquid diet. Quantitative real-time reverse transcription-PCR demonstrated that preproCRF mRNA was significantly upregulated by chronic ethanol exposure, whereas mRNA expression of CRF binding protein did not change. There were also no significant changes observed in any of the NMDA subunit mRNAs, although there was a trend toward greater NR2A mRNA expression during chronic ethanol exposure. Using Western blotting analysis we measured NMDA receptor subunit protein expression. Chronic ethanol exposure did not affect protein levels of the NR1 and NR2B subunits. Like the mRNA measures, chronic ethanol exposure did influence NR2A protein levels but the effects were modest. Our results demonstrate that NMDA receptor subunit mRNA and protein expressions are not strongly influenced by exposure to chronic ethanol. This suggests that the functional NMDA receptor adaptations identified in previous studies [Roberto, M., Schweitzer, P., Madamba, S. G., Stouffer, D. G., Parsons, L. H., & Siggins, G. R. (2004). Acute and chronic ethanol exposure alter glutamatergic transmission in rat central amygdala: an in vitro and in vivo analysis. J Neurosci 24, 1594-1603] are likely to be mediated by post-translational events. In contrast, enhanced levels of CRF during/after chronic ethanol exposure are likely to be mediated by increased levels of prepro CRF mRNA. Together, our findings suggest that adaptations to chronic ethanol exposure by proanxiety factors expressed in the central nucleus appear to be mediated by distinct cellular and molecular mechanisms.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets