The role of sociability in social instability stress: Behavioral, neuroendocrine and monoaminergic effects

Extensive literature has reported a link between social stress and mental health. In this complex relationship, individual strategies for coping with social stress are thought to have a possible modulating effect, with sociability being a key factor. Despite the higher incidence of affective disorders in females and sex-related neurochemical differences, female populations have been understudied. The aim of the present study was, therefore, to analyze the behavioral, neuroendocrine, and neurochemical effects of stress in female OF1 mice, paying special attention to social connectedness (female mice with high vs low sociability). To this end, subjects were exposed to the Chronic Social Instability Stress (CSIS) model for four weeks. Although female mice exposed to CSIS had increased arousal, there was no evidence of depressive-like behavior. Neither did exposure to CSIS affect corticosterone levels, although it did increase the MR/GR ratio by decreasing GR expression. Female mice exposed to CSIS had higher noradrenaline and dopamine levels in the hippocampus and striatum respectively, with a lower monoaminergic turnover, resulting in an increased arousal. CSIS increased serotonin levels in both the hippocampus and striatum. Similarly, CSIS was found to reduce kynurenic acid, 3-HK, and IDO and iNOS enzyme levels in the hippocampus. Interestingly, the observed decrease in IDO synthesis and the increased serotonin and dopamine levels in the striatum were only found in subjects with high sociability. These highly sociable female mice also had significantly lower levels of noradrenaline in the striatum after CSIS application. Overall, our model has produced neuroendocrine and neurochemical but not behavioral changes, so it has not allowed us to study sociability in depth. Therefore, a model that induces both molecular and behavioral phenotypes should be applied to determine the role of sociability.