Abstract
The establishment and maintenance of social dominance are critical for social stability and the survival and health of individual animals. Stress lead to depression and a decrease in the social status of depressed persons is a risk factor for suicide. Therefore, we explored the mechanistic and behavioral links among stress, depression, and social dominance and found that mice subjected to chronic restraint stress (CRS), an animal model of stress-induced depression, showed decreased social dominance as measured by a dominance tube test. Importantly, this submissive behavior was occluded by the antidepressant, fluoxetine, a selective serotonin reuptake inhibitor. It is known that social dominance is controlled by synaptic efficacy in the medial prefrontal cortex (mPFC) and that AMPA-type glutamate receptor (AMPA-R) is a key molecule for synaptic efficacy. We found that the phosphorylation on AMPA-R was bidirectionally changed by CRS and fluoxetine in the mPFC of mice with CRS. Moreover, we found a strong correlation between social dominance and AMPA-R phosphorylation that regulates synaptic efficacy by modulating the synaptic targeting of AMPA-R. Our correlational analysis of the behavior and biochemistry of the CRS model suggests that AMPA-R phosphorylation in the mPFC may serve as a biomarker of social dominance related to stress.
Highlights
Social dominance is a social structure of an animal group based on the relative social rank of its members[1,2]
Based on results from previous studies, we hypothesized that the AMPA-type glutamate receptor (AMPA-R) in the medial prefrontal cortex (mPFC) is a key molecule for controlling changes in social dominance induced by chronic stress and administration of an Selective serotonin reuptake inhibitors (SSRIs)
The AMPA-R phosphorylation was highly correlated with social dominance (Fig. 4h,i) and social behaviors that were induced by chronic stress (Supplementary Fig. S4)
Summary
Social dominance is a social structure of an animal group based on the relative social rank of its members[1,2]. An analytical study of the social context–dependent relationships between mouse dominance and plasma corticosterone, a stress hormone, found that subordinate males living in social hierarchies had significantly higher levels of plasma corticosterone than alpha males and pair-housed subordinate males[11]. These results suggest possible mechanistic and behavioral links among stress, depressive-like behaviors and social dominance. The functional synaptic activity in the mPFC has been considered to be important for mediating key symptoms of depression induced by chronic social stress[28]. Research has suggested a relationship between AMPA-R mediated neuronal activity changes in the mPFC and social dominance[26,31]
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