title: Response of the Tail of the Ventral Tegmental Area to Aversive Stimuli.
abstract: The GABAergic tail of the ventral tegmental area (tVTA), also named rostromedial tegmental nucleus (RMTg), exerts an inhibitory control on dopamine neurons of the VTA and substantia nigra. The tVTA has been implicated in avoidance behaviors, response to drugs of abuse, reward prediction error, and motor functions. Stimulation of the lateral habenula (LHb) inputs to the tVTA, or of the tVTA itself, induces avoidance behaviors, which suggests a role of the tVTA in processing aversive information. Our aim was to test the impact of aversive stimuli on the molecular recruitment of the tVTA, and the behavioral consequences of tVTA lesions. In rats, we assessed Fos response to lithium chloride (LiCl), β-carboline, naloxone, lipopolysaccharide (LPS), inflammatory pain, neuropathic pain, foot-shock, restraint stress, forced swimming, predator odor, and opiate withdrawal. We also determined the effect of tVTA bilateral ablation on physical signs of opiate withdrawal, and on LPS- and LiCl-induced conditioned taste aversion (CTA). Naloxone-precipitated opiate withdrawal induced Fos in μ-opioid receptor-positive (15%) and -negative (85%) tVTA cells, suggesting the presence of both direct and indirect mechanisms in tVTA recruitment during withdrawal. However, tVTA lesion did not impact physical signs of opiate withdrawal. Fos induction was also present with repeated, but not single, foot-shock delivery. However, such induction was mostly absent with other aversive stimuli. Moreover, tVTA ablation had no impact on CTA. Although stimulation of the tVTA favors avoidance behaviors, present findings suggest that this structure may be important to the response to some, but not all, aversive stimuli.
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.|Unitat Predepartamental de Medicina, Universitat Jaume I, Castelló de la Plana, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez-Catalán
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Faivre
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: Ipek
authors.initials: I
authors.lastname: Yalcin
authors.affiliation: Université de Strasbourg, Strasbourg, France.|Laboratoire de Neurosciences Cognitives et Adaptatives, Faculté de Psychologie, Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Muller
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Massotte
authors.affiliation: Université de Strasbourg, Strasbourg, France.|Laboratoire de Neurosciences Cognitives et Adaptatives, Faculté de Psychologie, Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Majchrzak
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Barrot
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009437:Neuralgia / Q000503:physiopathology; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology; D055696:Olfactory Perception / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D018692:Antimanic Agents; D002243:Carbolines; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; D017450:Receptors, Opioid, mu; D009270:Naloxone; C010262:norharman; D018021:Lithium Chloride