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 journalArticle

99 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 1 2002

ASJC Scopus subject areas

  • Medicine(all)

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    Hodge, C. W., Raber, J., McMahon, T., Walter, H., Sanchez-Perez, A. M., Foster Olive, M., Mehmert, K., Leslie Morrow, A., & Messing, R. O. (2002). Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε. Journal of Clinical Investigation, 110(7), 1003-1010. https://doi.org/10.1172/JCI200215903