title: 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 (PKCepsilon) 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 PKCepsilon activator, psiepsilonRACK, increased levels of pro-CRF, whereas reducing PKCepsilon levels through RNA interference blocked phorbol ester-stimulated increases in CRF. Local knockdown of amygdala PKCepsilon by RNA interference reduced anxiety-like behavior in wild-type mice. Furthermore, local infusion of CRF into the amygdala of PKCepsilon(-/-) mice increased their anxiety-like behavior. These results are consistent with a novel mechanism of PKCepsilon control over anxiety-like behavior through regulation of CRF in the amygdala.
authors: Department of Neurology, Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA.
authors: H M B
authors: HM
authors: Lesscher
authors: T
authors: T
authors: McMahon
authors: A W
authors: AW
authors: Lasek
authors: W-H
authors: WH
authors: Chou
authors: J
authors: J
authors: Connolly
authors: V
authors: V
authors: Kharazia
authors: R O
authors: RO
authors: Messing
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology / Q000502:physiology; D051744:Protein Kinase C-epsilon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D051744:Protein Kinase C-epsilon