Impaired social fear extinction in chronically stressed mice: Impact on inflammatory brain markers and the contribution of oxytocin.

Chronic psychosocial stress is a frequent burden in modern societies and risk factor for numerous somatic and affective disorders, including social anxiety disorder (SAD). Traumatic experiences after prolonged periods of stress exposure often trigger these diseases. Although human and animal studies support the hypothesis of an over-reactive immune system being critically involved in the pathogenesis of psychopathologies, the underlying mechanisms are not fully understood. Accordingly, immune-focused treatment options are lacking. The current study was performed in male C57BL/6 and CD1 mice using a combination of chronic subordinate colony housing (CSC), a mouse model for chronic psychosocial stress, and social fear conditioning (SFC), a mouse model for SAD. We can show that CSC prior to SFC exposure facilitates the manifestation of trauma-induced social avoidance and impairs its extinction, while increasing the release of inflammatory factors in the brain, especially in the amygdala. The neuropeptide oxytocin (OXT) with its profound pro-social, stress-buffering and anti-inflammatory effects has been suggested as a promising therapeutic option for stress-related diseases including SAD. Here, we can show that central OXT infusion protected against the observed behavioral phenotype, whereas the inflammatory parameters in the amygdala remained unchanged. Although further mechanistic studies are warranted, our findings indicate that chronic psychosocial stress aggravates the development of SAD-like symptoms caused by a traumatic social event and impairs its recovery. In addition, our data provide further evidence for stress- and trauma-protective effects of OXT but did not confirm its anti-inflammatory properties.