Interaction of CRF and kappa opioid systems on GABAergic neurotransmission in the mouse central amygdala.

Journal Article

The corticotropin-releasing factor (CRF) and kappa-opioid receptor (KOR) systems are both implicated in stress-related behaviors and drug dependence. Although previous studies suggest that antagonism of each system blocks aspects of experimental models of drug dependence, the possible interaction between these systems at the neuronal level has not been completely examined. We used an in vitro brain slice preparation to investigate the interaction of these two peptide systems on inhibitory neurotransmission in the central nucleus of the amygdala (CeA). Application of exogenous CRF increased the mean frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSC) by 20.2%, suggesting an increase in presynaptic GABA release. Although the pharmacological blockade of KORs by norBNI alone did not significantly affect mIPSC frequency, it significantly enhanced the effect of CRF (by 43.9%, P = 0.02). Similarly, the CRF effects in slices from KOR knockout (KO) mice (84.0% increase) were significantly greater than in wild-type (WT) mice (24.6%, P = 0.01), although there was no significant difference in baseline mIPSC frequency between slices from KOR KO and WT mice. The increase in CRF action in the presence of norBNI was abolished by a CRF-1 receptor antagonist but was unaffected by a CRF-2 receptor antagonist. We hypothesize that CRF facilitates the release of an endogenous ligand for KORs and that subsequent activation of KOR receptors modulates presynaptic effects of CRF in CeA. These results suggest that potential pharmacotherapies aimed at neurobehavioral and addictive disorders may need to involve both the KOR/dynorphin and the CRF systems in CeA.

Full Text

Duke Authors

Cited Authors

  • Kang-Park, M; Kieffer, BL; Roberts, AJ; Siggins, GR; Moore, SD

Published Date

  • November 2015

Published In

Volume / Issue

  • 355 / 2

Start / End Page

  • 206 - 211

PubMed ID

  • 26350161

Electronic International Standard Serial Number (EISSN)

  • 1521-0103

International Standard Serial Number (ISSN)

  • 0022-3565

Digital Object Identifier (DOI)

  • 10.1124/jpet.115.225870

Language

  • eng