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Men and women manifest different symptoms of depression and under current diagnostic criteria, depression is twice as prevalent in woman. However, little is known of the mechanisms contributing to these important sex differences. Sub-chronic variable stress (SCVS), a rodent model of depression, induces depression-like behaviors in female mice only, modeling clinical evidence of higher susceptibility to mood disorders in women. Accumulating evidence indicates that altered neuroplasticity of excitatory synapses in the nucleus accumbens (NAc) is a key pathophysiological feature of susceptibility to social stress in males. Here we investigated the effects of SCVS on pre- and post-synaptic protein levels and morphology of glutamatergic synapses of medium spiny neurons (MSNs) in the NAc of female and male mice. Animals underwent six-day exposure to alternating stressors including shock, tail suspension and …