Research article summary (published 30 Oct 1999):

Supersensitivity to allosteric GABA(A) receptor modulators and alcohol in mice lacking PKCepsilon.

Full Abstract

Several of the actions of ethanol are mediated by gamma-aminobutyrate type A (GABA(A)) receptors. Here we demonstrated that mutant mice lacking protein kinase C epsilon (PKCepsilon) were more sensitive than wild-type littermates to the acute behavioral effects of ethanol and other drugs that allosterically activate GABA(A) receptors. GABA(A) receptors in membranes isolated from the frontal cortex of PKCepsilon null mice were also supersensitive to allosteric activation by ethanol and flunitrazepam. In addition, these mutant mice showed markedly reduced ethanol self-administration. These findings indicate that inhibition of PKCepsilon increases sensitivity of GABA(A) receptors to ethanol and allosteric modulators. Pharmacological agents that inhibit PKCepsilon may be useful for treatment of alcoholism and may provide a non-sedating alternative for enhancing GABA(A) receptor function to treat other disorders such as anxiety and epilepsy.

Author information

Author/s: Hodge, C W (CW); Mehmert, K K (KK); Kelley, S P (SP); McMahon, T (T); Haywood, A (A); Olive, M F (MF); Wang, D (D); Sanchez-Perez, A M (AM); Messing, R O (RO);

Affiliation: Department of Neurology and Ernest Gallo Clinic and Research Center, University of California, San Francisco 94110, USA. chodge(-atsign-)itsa.ucsf. edu

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Nature neuroscience (Nat Neurosci), published in UNITED STATES. (Language: eng)

Reference: 1999-Nov; vol 2 (issue 11) : pp 997-1002

Dates: Created 1999/11/19; Completed 1999/11/19; Revised 2007/11/15;

PMID: 10526339, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Allosteric Regulation Animals Behavior, Animal - drug effects Cerebellum - drug effects Cerebral Cortex - drug effects Corpus Striatum - drug effects Ethanol - pharmacology Female Flunitrazepam - pharmacology GABA Modulators - pharmacology

Isoenzymes - genetics Male Mice Mice, Inbred C57BL Mutation Protein Kinase C - genetics Protein Kinase C-epsilon Radioligand Assay Receptors, GABA-A - drug effects Self Administration

Associated Chemicals: GABA Modulators (0) ; Isoenzymes (0) ; Receptors, GABA-A (0) ; Flunitrazepam (1622-62-4) ; Ethanol (64-17-5) ; Prkce protein, mouse (EC 2.7.1.-) ; Protein Kinase C-epsilon (EC 2.7.1.37) ; Protein Kinase C (EC 2.7.11.13)

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