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

TitleInteraction of CRF and kappa opioid systems on GABAergic neurotransmission in the mouse central amygdala.
Publication TypeJournal Article
Year of Publication2015
AuthorsKang-Park M, Kieffer BL, Roberts AJ, Siggins GR, Moore SD
JournalJ Pharmacol Exp Ther
Volume355
Issue2
Pagination206-11
Date Published2015 Nov
ISSN1521-0103
KeywordsAnimals, Central Amygdaloid Nucleus, Corticotropin-Releasing Hormone, gamma-Aminobutyric Acid, Inhibitory Postsynaptic Potentials, Mice, Inbred C57BL, Mice, Knockout, Miniature Postsynaptic Potentials, Naltrexone, Receptors, Corticotropin-Releasing Hormone, Receptors, Opioid, kappa, Synaptic Transmission
Abstract

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.

DOI10.1124/jpet.115.225870
Alternate JournalJ. Pharmacol. Exp. Ther.
PubMed ID26350161
PubMed Central IDPMC4613963
Grant ListU01 AA013498 / AA / NIAAA NIH HHS / United States
R01 DA03665 / DA / NIDA NIH HHS / United States
AA16658 / AA / NIAAA NIH HHS / United States
I01 BX001271 / BX / BLRD VA / United States
R01 DA003665 / DA / NIDA NIH HHS / United States
U01 AA016658 / AA / NIAAA NIH HHS / United States

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