title: mGluR5 in the nucleus accumbens is critical for promoting resilience to chronic stress.
abstract: Resilience to aversive events has a central role in determining whether stress leads to the development of depression. mGluR5 has been implicated in the pathophysiology of depression, but the effect of mGluR5 activity on stress resilience remains unexplored. We found that mGluR5(-/-) (also known as Grm5(-/-)) mice displayed more depression-like behaviors (for example, learned helplessness, social withdrawal and anhedonia) than control mice following exposure to various stressful stimuli. Lentiviral 'rescue' of mGluR5 in the nucleus accumbens (NAc) decreased these depression-like behaviors in mGluR5(-/-) mice. In the NAc, ΔFosB, whose induction promotes stress resilience, failed to be upregulated by stress in mGluR5(-/-) mice. Notably, targeted pharmacological activation of mGluR5 in the NAc increased ΔFosB expression. Our findings point to an essential role for mGluR5 in promoting stress resilience and suggest that a defect in mGluR5-mediated signaling in the NAc may represent an endophenotype for stress-induced depression.
authors.affiliation: Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Obin
authors.initials: O
authors.lastname: Kwon
authors.affiliation: Department of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jee In
authors.initials: JI
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Somin
authors.initials: S
authors.lastname: Kwon
authors.affiliation: 1] Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. [2] Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Seoul, Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Choi
authors.affiliation: 1] Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. [2] Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Goo
authors.initials: DG
authors.lastname: Kim
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003863:Depression / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D058068:Endophenotypes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism / Q000502:physiology*; D055500:Resilience, Psychological; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*
chemical_list: C483819:Fosb protein, mouse; C578936:Grm5 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D064529:Receptor, Metabotropic Glutamate 5