Diazépam | EPFL Graph Search

Le diazépam est un médicament de la famille des benzodiazépines. Il possède des propriétés anxiolytiques, sédatives, amnésiantes et hypnotiques. Néanmoins, en raison de ses effets importants de somnolence résiduelle le lendemain matin, il est de moins en moins utilisé comme hypnotique en clinique. Comme toutes les molécules appartenant à la famille des benzodiazépines, le diazépam possède également des propriétés anticonvulsivantes et myorelaxantes. Le diazépam est notamment utile dans le cadre du traitement des crises comitiales et épileptiques. C’est un médicament de choix pour son métabolisme rapide ainsi que pour ses vertus myorelaxantes, à l’instar d'autres benzodiazépines comme le tétrazépam (Myolastan, retiré du marché européen en juillet 2013 et seule benzodiazépine à avoir reçu une autorisation de mise sur le marché pour le traitement d'appoint des contractures musculaires). Commercialisé en 1963 sous la marque Valium par les laboratoires Hoffmann-La Roche, c'est la seconde

Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of accumbal dopamine D1 receptors

Sonia Abad Florensa, Carlos Canto Alvarez, Jocelin Grosse, Marie-Isabelle Guillot de Suduiraut, Fiona Hollis, Laura Lozano Montes, Maria del Carmen Sandi Perez, Michael van der Kooij, Ioannis Zalachoras, Olivia Zanoletti

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

Nature Publishing Group2018

Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of accumbal dopamine D1 receptors

Nature Publishing Group2018