Involvement of DR→mPFC 5-HTergic neural projections in changes of social exploration behaviors caused by adult chronic social isolation in mice

Social contacts play an important role in the development and survival of social animals. Social isolation (SI) at adolescence often induces abnormalities in many kinds of behaviors. This study assessed whether five weeks of continuous SI at adulthood could alter social behaviors and whether dorsal raphe nucleus (DR) to medial prefrontal cortex (mPFC) 5-HT neural projections were involved in this alteration in C57BL/6J adult male mice. The present study found that five weeks chronic social isolation (CSI) at adulthood increased mounting and sniffing behaviors in resident-intruder test, and lengthened duration staying in interaction zone of stranger cage in the three-chamber social preference test. CSI also reduced the release of 5-HT in the mPFC detected by 5-HT 1.0 sensor and measured by in vivo fiber photometry test. Meanwhile, the c-Fos expression indicated that CSI reduced the activity of serotonergic neurons. Chemogenetic activation of DR-mPFC 5-HTergic projection reduced sniffing of CSI mice in the resident-intruder test, but didn't significantly affect mounting behavior. It also decreased the interaction time during the three-chamber social preference test. Thus, 5-HT neural projections from the DR to the mPFC are involved in changes of social exploration behaviors induced by CSI at adulthood.