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Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress

Authors :
Abigail M Polter
Kelsey Barcomb
Rudy W Chen
Paige M Dingess
Nicholas M Graziane
Travis E Brown
Julie A Kauer
Source :
eLife, Vol 6 (2017)
Publication Year :
2017
Publisher :
eLife Sciences Publications Ltd, 2017.

Abstract

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also provide evidence that constitutive activity of κORs governs the prolonged reinstatement to cocaine-seeking observed after cold water swim stress. Together, our studies indicate that stress-induced constitutive activation is a novel mechanism of κOR regulation that plays a critical role in reinstatement of drug seeking.

Details

Language :
English
ISSN :
2050084X
Volume :
6
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.59099f1110247929b59f1309fdddb6f
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.23785