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.
Key Words
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Article info
Publication history
Published online: January 09, 2012
Accepted:
November 9,
2011
Received in revised form:
October 26,
2011
Received:
July 27,
2011
Footnotes
Authors CL and KEP contributed equally to this work.
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
