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mGluR5 in the nucleus accumbens is critical for promoting resilience to chronic stress

 Sora Shin  ;  Obin Kwon  ;  Jee In Kang  ;  Somin Kwon  ;  Sora Oh  ;  Jiwon Choi  ;  Chul Hoon Kim  ;  Dong Goo Kim 
 NATURE NEUROSCIENCE, Vol.18(7) : 1017-1024, 2015 
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Animals ; Behavior, Animal/physiology* ; Depression/etiology ; Depression/metabolism* ; Disease Models, Animal ; Endophenotypes ; Male ; Mice ; Mice, Inbred C57BL ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism* ; Proto-Oncogene Proteins c-fos/metabolism* ; Receptor, Metabotropic Glutamate 5/metabolism ; Receptor, Metabotropic Glutamate 5/physiology* ; Resilience, Psychological* ; Signal Transduction/physiology* ; Stress, Psychological/complications ; Stress, Psychological/metabolism*
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.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Jee In(강지인) ORCID logo https://orcid.org/0000-0002-2818-7183
Kwon, O Bin(권오빈)
Kim, Dong Goo(김동구)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Shin, So Ra(신소라)
Oh, So Ra(오소라)
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