References
Query Results -- Details
MGI Accession ID: MGI:1346755
J Number: J:58126
Other Accession IDs:
Title: Supersensitivity to allosteric GABA(A) receptor modulators and alcohol in mice lacking PKCepsilon.
Authors: Hodge CW; Mehmert KK; Kelley SP; McMahon T; Haywood A; Olive MF; Wang D; Sanchez-Perez AM; Messing RO
Journal: Nat Neurosci
Volume: 2
Issue: 11
Date: 1999 Nov
Year: 1999
Pages: 997-1002
Review Status: Peer Reviewed
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.
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