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Biol Psychiatry. 2012 Apr 15;71(8):725-32. doi: 10.1016/j.biopsych.2011.11.015. Epub 2012 Jan 5.

Presynaptic inhibition of gamma-aminobutyric acid release in the bed nucleus of the stria terminalis by kappa opioid receptor signaling.

Author information

  • 1Curriculum in Neurobiology, School of Medicine, University of North Carolina-Chapel Hill, NC 27599, USA.

Abstract

BACKGROUND:

The kappa opioid receptor (KOR) and its endogenous agonist, the neuropeptide dynorphin, are a critical component of the central stress system. Both dynorphin and KOR are expressed in the bed nucleus of the stria terminalis (BNST), a brain region associated with anxiety and stress. This suggests that KOR activation in this region may play a role in the regulation of emotional behaviors. To date, however, there has been no investigation of the ability of KOR to modulate synaptic transmission in the BNST.

METHODS:

We used whole-cell patch-clamp recordings from acutely prepared mouse brain slices to examine the actions of KOR on inhibitory transmission in the BNST. Additionally, we used neurochemical and pathway-specific optogenetic manipulations to selectively stimulate gamma-aminobutyric acid (GABA)ergic fibers from the central nucleus of the amygdala (CeA) to the BNST.

RESULTS:

We found that activation of KOR reduced GABAergic transmission through a presynaptic mechanism. Furthermore, we examined the signal transduction pathways that mediate this inhibition and provide the first functional information implicating extracellular signal-regulated kinase in KOR-mediated presynaptic modulation. Moreover, we found that at KOR signaling robustly reduced inhibitory synaptic transmission in the CeA to BNST pathway.

CONCLUSIONS:

Together, these results demonstrate that KOR provides important inhibitory control over presynaptic GABAergic signaling within the BNST and provides the first direct functional demonstration of KOR-sensitive long-range GABAergic connections between the CeA and the BNST.

Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PMID:
22225848
[PubMed - indexed for MEDLINE]
PMCID:
PMC3314138
Free PMC Article

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