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Habenular Neurons Expressing Mu Opioid Receptors Promote Negative Affect in a Projection-Specific Manner.
Bailly, Julie; Allain, Florence; Schwartz, Eric; Tirel, Chloé; Dupuy, Charles; Petit, Florence; Diana, Marco A; Darcq, Emmanuel; Kieffer, Brigitte L.
Afiliación
  • Bailly J; Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
  • Allain F; Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada; INSERM U1114, Department of Psychiatry, University of Strasbourg, Strasbourg, France.
  • Schwartz E; Sorbonne Université, CNRS, INSERM, Neurosciences Paris Seine-Institut de Biologie Paris Seine, Paris, France.
  • Tirel C; Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
  • Dupuy C; Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
  • Petit F; Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
  • Diana MA; Sorbonne Université, CNRS, INSERM, Neurosciences Paris Seine-Institut de Biologie Paris Seine, Paris, France.
  • Darcq E; Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada; INSERM U1114, Department of Psychiatry, University of Strasbourg, Strasbourg, France.
  • Kieffer BL; Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada; INSERM U1114, Department of Psychiatry, University of Strasbourg, Strasbourg, France. Electronic address: brigitte.kieffer@unistra.fr.
Biol Psychiatry ; 93(12): 1108-1117, 2023 06 15.
Article en En | MEDLINE | ID: mdl-36496267
BACKGROUND: The mu opioid receptor (MOR) is central to hedonic balance and produces euphoria by engaging reward circuits. MOR signaling may also influence aversion centers, notably the habenula (Hb), where the receptor is highly dense. Our previous data suggest that the inhibitory activity of MOR in the Hb may limit aversive states. To investigate this hypothesis, we tested whether neurons expressing MOR in the Hb (Hb-MOR neurons) promote negative affect. METHODS: Using Oprm1-Cre knockin mice, we combined tracing and optogenetics with behavioral testing to investigate consequences of Hb-MOR neuron stimulation for approach/avoidance (real-time place preference), anxiety-related responses (open field, elevated plus maze, and marble burying), and despair-like behavior (tail suspension). RESULTS: Optostimulation of Hb-MOR neurons elicited avoidance behavior, demonstrating that these neurons promote aversive states. Anterograde tracing showed that, in addition to the interpeduncular nucleus, Hb-MOR neurons project to the dorsal raphe nucleus. Optostimulation of Hb-MOR/interpeduncular nucleus terminals triggered avoidance and despair-like responses with no anxiety-related effect, whereas light-activation of Hb-MOR/dorsal raphe nucleus terminals increased levels of anxiety with no effect on other behaviors, revealing 2 dissociable pathways controlling negative affect. CONCLUSIONS: Together, the data demonstrate that Hb neurons expressing MOR facilitate aversive states via 2 distinct Hb circuits, contributing to despair-like behavior (Hb-MOR/interpeduncular nucleus) and anxiety (Hb-MOR/dorsal raphe nucleus). The findings support the notion that inhibition of these neurons by either endogenous or exogenous opioids may relieve negative affect, a mechanism that would have implications for hedonic homeostasis and addiction.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Opioides mu / Habénula Límite: Animals Idioma: En Revista: Biol Psychiatry Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Opioides mu / Habénula Límite: Animals Idioma: En Revista: Biol Psychiatry Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos