Ablation of the tail of the ventral tegmental area compensates symptoms in an experimental model of Parkinson’s disease.
Neurobiology of Disease. 2020-06-01; 139: 104818
DOI: 10.1016/j.nbd.2020.104818
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1. Neurobiol Dis. 2020 Jun;139:104818. doi: 10.1016/j.nbd.2020.104818. Epub 2020 Feb
20.
Ablation of the tail of the ventral tegmental area compensates symptoms in an
experimental model of Parkinson’s disease.
Faivre F(1), Sánchez-Catalán MJ(2), Dovero S(3), Bido S(3), Joshi A(4), Bezard
E(3), Barrot M(5).
Author information:
(1)Centre National de la Recherche Scientifique, Université de Strasbourg,
Institut des Neurosciences Cellulaires et Intégratives, F-67000 Strasbourg,
France.
(2)Centre National de la Recherche Scientifique, Université de Strasbourg,
Institut des Neurosciences Cellulaires et Intégratives, F-67000 Strasbourg,
France; Unitat Predepartemental de Medicina, Universitat Jaume I Castelló de la
Plana, Spain.
(3)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Centre National de la Recherche Scientifique, Institut
des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
(4)Centre National de la Recherche Scientifique, Université de Strasbourg,
Institut des Neurosciences Cellulaires et Intégratives, F-67000 Strasbourg,
France; Department of Endocrinology and Metabolism, Amsterdam University Medical
Centers, University of Amsterdam, Amsterdam, Netherlands.
(5)Centre National de la Recherche Scientifique, Université de Strasbourg,
Institut des Neurosciences Cellulaires et Intégratives, F-67000 Strasbourg,
France. Electronic address: .
Parkinson’s disease is a neurodegenerative disorder partly caused by the loss of
the dopamine neurons of the nigrostriatal pathway. It is accompanied by motor as
well as non-motor symptoms, including pain and depression. The tail of the
ventral tegmental area (tVTA) or rostromedial tegmental nucleus (RMTg) is a
GABAergic mesopontine structure that acts as a major inhibitory brake for the
substantia nigra pars compacta (SNc) dopamine cells, thus controlling their
neuronal activity and related motor functions. The present study tested the
influence of suppressing this tVTA brake on motor and non-motor symptoms in a rat
model of Parkinson’s disease. Using behavioral approaches, we showed that male
Sprague-Dawley rats with bilateral and partial 6-hydroxydopamine SNc lesion
displayed motor impairments in the rotarod test, impairments that were no more
present following a co-lesion of the tVTA. Using a larger set of behavioral
tests, we then showed that such SNc lesion also led to non-motor symptoms,
including lower body weight, lower mechanical nociceptive thresholds in the
forceps test and lower thermal nociceptive thresholds in the incremented
hot-plate test, and a decreased sucrose preference in a 2-bottle choice paradigm.
The excitotoxic co-lesion of the tVTA led to compensation of body weight,
mechanical nociceptive thresholds and anhedonia-like behavior. These findings
illustrate the major influence that the tVTA exerts on the dopamine system,
modulating the motor and non-motor symptoms related to a partial loss of dopamine
cells.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2020.104818
PMID: 32087289
Conflict of interest statement: Declaration of Competing Interest None.