Your browser doesn't support javascript.
loading
Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.
van der Kooij, M A; Hollis, F; Lozano, L; Zalachoras, I; Abad, S; Zanoletti, O; Grosse, J; Guillot de Suduiraut, I; Canto, C; Sandi, C.
Afiliação
  • van der Kooij MA; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Hollis F; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Lozano L; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Zalachoras I; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Abad S; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Zanoletti O; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Grosse J; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Guillot de Suduiraut I; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Canto C; Nestlé Institute of Health Sciences SA, Lausanne, Switzerland.
  • Sandi C; Laboratory of Behavioral Genetics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Mol Psychiatry ; 23(3): 569-578, 2018 03.
Article em En | MEDLINE | ID: mdl-28727688
Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ansiedade / Área Tegmentar Ventral / Diazepam Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ansiedade / Área Tegmentar Ventral / Diazepam Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article