Phasic Dopamine Signals in the Nucleus Accumbens that Cause Active Avoidance Require Endocannabinoid Mobilization in the Midbrain.

Autor:	Wenzel JM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Oleson EB; Department of Psychology, University of Colorado, Denver, CO 80204, USA., Gove WN; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Cole AB; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Gyawali U; Department of Pharmacology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA., Dantrassy HM; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Bluett RJ; Vanderbilt Brain Institute and Department of Psychiatry, Vanderbilt University, Nashville, TN 37235, USA., Dryanovski DI; Electrophysiology Research Section, Cellular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD 21224, USA., Stuber GD; Department of Psychiatry and Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA., Deisseroth K; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA., Mathur BN; Department of Pharmacology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA., Patel S; Vanderbilt Brain Institute and Department of Psychiatry, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt School of Medicine and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37235, USA., Lupica CR; Electrophysiology Research Section, Cellular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD 21224, USA., Cheer JF; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: jcheer@som.umaryland.edu.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2018 May 07; Vol. 28 (9), pp. 1392-1404.e5. Date of Electronic Publication: 2018 Apr 19.
DOI:	10.1016/j.cub.2018.03.037
Abstrakt:	Phasic dopamine (DA) release accompanies approach toward appetitive cues. However, a role for DA in the active avoidance of negative events remains undetermined. Warning signals informing footshock avoidance are associated with accumbal DA release, whereas depression of DA is observed with unavoidable footshock. Here, we reveal a causal role of phasic DA in active avoidance learning; specifically, optogenetic activation of DA neurons facilitates avoidance, whereas optical inhibition of these cells attenuates it. Furthermore, stimulation of DA neurons during presentation of a fear-conditioned cue accelerates the extinction of a passive defensive behavior (i.e., freezing). Dopaminergic control of avoidance requires endocannabinoids (eCBs), as perturbing eCB signaling in the midbrain disrupts avoidance, which is rescued by optical stimulation of DA neurons. Interestingly, once the avoidance task is learned, neither DA nor eCB manipulations affect performance, suggesting that once acquisition occurs, expression of this behavior is subserved by other anatomical frameworks. Our findings establish an instrumental role for DA release in learning active responses to aversive stimuli and its control by eCB signaling. (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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