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The susceptibility to chronic social defeat stress is related to low hippocampal extrasynaptic NMDA receptor function.
Tse, Yiu Chung; Lopez, Joëlle; Moquin, Alexandre; Wong, Shui-Ming Alice; Maysinger, Dusica; Wong, Tak Pan.
Afiliación
  • Tse YC; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montreal, QC, Canada.
  • Lopez J; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montreal, QC, Canada.
  • Moquin A; Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada.
  • Wong SA; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montreal, QC, Canada.
  • Maysinger D; Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada.
  • Wong TP; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montreal, QC, Canada. takpan.wong@mcgill.ca.
Neuropsychopharmacology ; 44(7): 1310-1318, 2019 06.
Article en En | MEDLINE | ID: mdl-30723288
N-methyl-D-aspartate receptors (NMDARs) have been highly implicated in the pathogenesis and treatment of depression. While NMDARs can be found inside and outside glutamate synapses, it remains unclear if NMDARs at synaptic (sNMDAR) and extrasynaptic locations (exNMDAR) play different roles in the formation of depression-related behaviors. Using chronic social defeat stress (CSDS), an animal model for anxiety- and depression-related behaviors, we found that mice susceptible to CSDS exhibited low hippocampal exNMDAR function. Raising exNMDAR function by enhancing the release of glutamate from astrocytic cystine-glutamate antiporters or targeting extrasynaptic receptors with agonist-coated gold nanoparticles that cannot enter the synaptic cleft prevented social avoidance behavior in stressed mice. Interestingly, ketamine, which is a fast-acting antidepressant, exhibited stronger blockade to sNMDARs than to exNMDARs. These findings suggest that the susceptibility and resilience of mice toward CSDS is related to low and high exNMDAR function in the hippocampus, respectively. Enhancing exNMDAR function could be a novel treatment approach for mood and anxiety disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ansiedad / Estrés Psicológico / Receptores de N-Metil-D-Aspartato / Depresión / Región CA1 Hipocampal / Neuronas Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Neuropsychopharmacology Asunto de la revista: NEUROLOGIA / PSICOFARMACOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ansiedad / Estrés Psicológico / Receptores de N-Metil-D-Aspartato / Depresión / Región CA1 Hipocampal / Neuronas Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Neuropsychopharmacology Asunto de la revista: NEUROLOGIA / PSICOFARMACOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido