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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Dynorphins / metabolism*
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Patch-Clamp Techniques
  • Receptors, Opioid, kappa / metabolism*
  • Septal Nuclei / metabolism*
  • Signal Transduction / physiology
  • Synaptic Transmission / physiology*
  • gamma-Aminobutyric Acid / metabolism*


  • Receptors, Opioid, kappa
  • gamma-Aminobutyric Acid
  • Dynorphins
  • Mitogen-Activated Protein Kinases