TY - JOUR AU - Hodge, Clyde W. AU - Raber, Jacob AU - McMahon, Thomas AU - Walter, Helen AU - Sanchez-Perez, Ana Maria AU - Olive, M. Foster AU - Mehmert, Kristin AU - Morrow, A. Leslie AU - Messing, Robert O. T1 - Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε PY - 2002/10/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI15903 VL - 110 IS - 7 UR - https://doi.org/10.1172/JCI15903 SP - 1003 EP - 1010 PB - The American Society for Clinical Investigation ER -