Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε

Clyde W. Hodge, Jacob Raber, Thomas McMahon, Helen Walter, Ana Maria Sanchez-Perez, M. Foster Olive, Kristin Mehmert, A. Leslie Morrow, Robert O. Messing

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Mice lacking protein kinase Cε (PKCε) are supersensitive to positive allosteric modulators of gamma aminobutyrate type A (GABAA) receptors. Since many of these compounds are anxiolytic, we examined whether anxiety-like behavior is altered in these mice. PKCε-null mice showed reduced anxiety-like behavior and reduced levels of the stress hormones corticosterone and adrenocorticotrophic hormone (ACTH). This was associated with increased sensitivity to neurosteroid modulators of GABAA receptors. Treatment of PKCε-null mice with the GABAA receptor antagonist bicuculline restored corticosterone levels and anxiety-like behavior to wild-type levels. These results suggest that increased GABAA receptor sensitivity to neurosteroids contributes to reduced anxiety-like behavior and stress hormone responses in PKCε-null mice. The findings also suggest PKCε as a possible therapeutic target for development of anxiolytics.

Original languageEnglish (US)
Pages (from-to)1003-1010
Number of pages8
JournalJournal of Clinical Investigation
Volume110
Issue number7
DOIs
StatePublished - Oct 2002
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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