Serotonin Signaling Trough Prelimbic 5-HT1A Receptors Modulates CSDS-Induced Behavioral Changes in Adult Female Voles

摘要

Background Most previous studies have focused on the effects of social defeat in male juvenile individuals. Whether chronic social defeat stress 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 chronic social defeat stress on anxiety- and depression-like behaviors 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 behaviors. Meanwhile, defeated voles exhibited increased neural activity in the prelimbic cortex of the medial prefrontal cortex. Furthermore, chronic social defeat stress reduced serotonin projections and levels of serotonin 1A receptors in the medial prefrontal cortex-prelimbic cortex. Intra-prelimbic cortex microinjections of the serotonin 1A receptor agonist 8-OH-DPAT reversed the alterations in emotional behaviors, whereas injections of the serotonin 1A receptor antagonist WAY-100635 into the prelimbic cortex of control voles increased the levels of anxiety- and depression-like behaviors. Conclusions Taken together, our results demonstrated that chronic social defeat stress increased anxiety- and depression-like behaviors in adult female voles, and these effects were mediated by the action of serotonin on the serotonin 1A receptors in the prelimbic cortex. The serotonin system may be a promising target to treat emotional disorders induced by chronic social defeat stress. 5-HT1A receptor , mPFC , CSDS , emotional disorders , mandarin voles Significance Statement Studies indicate that women may have higher susceptibility to violence and higher rates of stress-associated disorders compared to men. However, most previous studies have focused on social defeat in male juvenile individuals. Whether CSDS at adulthood affects female emotion and its underlying mechanism remains unclear. Recent evidence has indicated that serotonergic transmission and the 5-HTsub1A/subR in the mPFC has an important inhibitory effect in anxiety and depression. The present study demonstrated that the CSDS increased anxiety- and depressive-like behaviors in adult female voles, and these effects were mediated by the action of 5-HT on the 5-HTsub1A/subR in the mPFC. These findings show that the serotonin system may be a promising target to treat emotional disorders in women induced by CSDS.