Serotonin signaling trough prelimbic 5-HT1A receptors modulates CSDS induces behavioural changes in adult female voles.

Background: Most previous studies have focused on the effects of social defeat in male juvenile individuals. Whether chronic social defeat stress (CSDS) in adulthood affects female emotion and the underlying mechanisms remains unclear.

Methods: Using highly aggressive adult female mandarin voles (Microtus mandarinus), the present study aimed to determine the effects of CSDS on anxiety- and depression-like behaviours in adult female rodents and investigate the neurobiological mechanisms underlying these effects.

Results: Exposure of adult female voles to social defeat stress for 14 days reduced the time spent in the central area of the open field test and in the open arms of the elevated plus maze and lengthened the immobility time in the tail suspension and forced swimming tests, indicating increased anxiety- and depression-like behaviours. Meanwhile, defeated voles exhibited increased neural activity in the prelimbic (PrL) cortex of the medial prefrontal cortex (mPFC). Furthermore, CSDS reduced serotonin (5-HT) projections and levels of serotonin 1A receptors (5-HT1AR) in the mPFC-PrL. Intra-PrL microinjections of the 5-HT1AR agonist 8-OH-DPAT reversed the alterations in emotional behaviours, whereas injections of the 5-HT1AR antagonist WAY-100635 into the PrL of control voles increased the levels of anxiety- and depression-like behaviours.

Conclusions: Taken together, our results demonstrated that CSDS increased anxiety- and depression-like behaviours in adult female voles, and these effects were mediated by the action of 5-HT on the 5-HT1AR in the PrL. The serotonin system may be a promising target to treat emotional disorders induced by CSDS.