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

97 Citations (Scopus)

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

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Aminobutyrates
Protein Kinase C
Neurotransmitter Agents
Anxiety
Hormones
Anti-Anxiety Agents
Corticosterone
Bicuculline
Adrenocorticotropic Hormone

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε. / Hodge, Clyde W.; Raber, Jacob; McMahon, Thomas; Walter, Helen; Sanchez-Perez, Ana Maria; Foster Olive, M.; Mehmert, Kristin; Leslie Morrow, A.; Messing, Robert O.

In: Journal of Clinical Investigation, Vol. 110, No. 7, 10.2002, p. 1003-1010.

Research output: Contribution to journalArticle

Hodge, CW, Raber, J, McMahon, T, Walter, H, Sanchez-Perez, AM, Foster Olive, M, Mehmert, K, Leslie Morrow, A & Messing, RO 2002, 'Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε', Journal of Clinical Investigation, vol. 110, no. 7, pp. 1003-1010. https://doi.org/10.1172/JCI200215903
Hodge, Clyde W. ; Raber, Jacob ; McMahon, Thomas ; Walter, Helen ; Sanchez-Perez, Ana Maria ; Foster Olive, M. ; Mehmert, Kristin ; Leslie Morrow, A. ; Messing, Robert O. / Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε. In: Journal of Clinical Investigation. 2002 ; Vol. 110, No. 7. pp. 1003-1010.
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