title: Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress.
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.
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Abigail M
authors.identifier: 0000-0003-0151-0996
authors.initials: AM
authors.lastname: Polter
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Barcomb
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Rudy W
authors.initials: RW
authors.lastname: Chen
authors.affiliation: Neuroscience Program, University of Wyoming, Laramie, United States.|University of Wyoming, School of Pharmacy, Laramie, United States.
authors.forename: Paige M
authors.initials: PM
authors.lastname: Dingess
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Graziane
authors.affiliation: Neuroscience Program, University of Wyoming, Laramie, United States.|University of Wyoming, School of Pharmacy, Laramie, United States.
authors.forename: Travis E
authors.initials: TE
authors.lastname: Brown
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Julie A
authors.identifier: 0000-0002-3362-1642
authors.initials: JA
authors.lastname: Kauer
mesh_terms: D000818:Animals; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013312:Stress, Physiological; D013569:Synapses / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000502:physiology*
chemical_list: D017473:Receptors, Opioid, kappa
keywords: GABA; Kappa Opioid Receptor; Stress; Synaptic Plasticity; VTA; dopamine; neuroscience; rat