Back to Search
Start Over
Voluntary wheel running promotes resilience to chronic social defeat stress in mice: a role for nucleus accumbens ΔFosB.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2018 Aug; Vol. 43 (9), pp. 1934-1942. Date of Electronic Publication: 2018 May 24. - Publication Year :
- 2018
-
Abstract
- Elucidating mechanisms by which physical exercise promotes resilience, the brain's ability to cope with prolonged stress exposure while maintaining normal psychological functioning, is a major research challenge given the high prevalence of stress-related mental disorders, including major depressive disorder. Chronic voluntary wheel running (VWR), a rodent model that mimics aspects of human physical exercise, induces the transcription factor ΔFosB in the nucleus accumbens (NAc), a key reward-related brain area. ΔFosB expression in NAc modulates stress susceptibility. Here, we explored whether VWR induction of NAc ΔFosB promotes resilience to chronic social defeat stress (CSDS). Male young-adult C57BL/6J mice were single housed for up to 21 d with or without running wheels and then subjected to 10 d of CSDS. Stress-exposed sedentary mice developed a depressive-like state, characterized by anhedonia and social avoidance, whereas stress-exposed mice that had been wheel running showed resilience. Functional inhibition of NAc ΔFosB during VWR, by viral-mediated overexpression of a transcriptionally inactive JunD mutant, reinstated susceptibility to CSDS. Within the NAc, VWR induction of ΔFosB was CREB-dependent, associated with altered dendritic morphology, and medium spiny neuron (MSN) subtype specific in the NAc core and shell subregions. Finally, when mice performed VWR following the onset of CSDS-induced social avoidance, VWR normalized such behavior. These data indicate that VWR promoted resilience to CSDS, and suggest that sustained induction of ΔFosB in the NAc underlies, at least in part, the stress resilience mediated by VWR. These findings provide a potential framework for the development of treatments for stress-associated mental illnesses based on physical exercise.
- Subjects :
- Anhedonia physiology
Animals
Dendritic Spines metabolism
Dendritic Spines pathology
Depression metabolism
Depression pathology
Dominance-Subordination
Male
Mice, Inbred C57BL
Nucleus Accumbens pathology
Sedentary Behavior
Stress, Psychological pathology
Transcription, Genetic
Volition
Nucleus Accumbens metabolism
Resilience, Psychological
Running physiology
Running psychology
Stress, Psychological metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1740-634X
- Volume :
- 43
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29875450
- Full Text :
- https://doi.org/10.1038/s41386-018-0103-z