Amygdala protein kinase C epsilon regulates corticotropin-releasing factor and anxiety-like behavior

Abstract

Corticotropin-releasing factor (CRF), its receptors, and signaling pathways that regulate CRF expression and responses are areas of intense investigation for new drugs to treat affective disorders. Here, we report that protein kinase C epsilon (PKCε) null mutant mice, which show reduced anxiety-like behavior, have reduced levels of CRF messenger RNA and peptide in the amygdala. In primary amygdala neurons, a selective PKCε activator, ψεRACK, increased levels of pro-CRF, whereas reducing PKCε levels through RNA interference blocked phorbol ester-stimulated increases in CRF. Local knockdown of amygdala PKCε by RNA interference reduced anxiety-like behavior in wild-type mice. Furthermore, local infusion of CRF into the amygdala of PKCε-/- mice increased their anxiety-like behavior. These results are consistent with a novel mechanism of PKCε control over anxiety-like behavior through regulation of CRF in the amygdala. © 2007 The Authors.