Chronic defeat stress induces monoamine level dysregulation in the prefrontal cortex but not in the hippocampus of OF1 male mice.

Chronic social stress can increase susceptibility to chronic diseases such as depression. One of the most used models to study the physiological mechanisms and behavioral outcomes of this type of stress is chronic defeat stress (CDS) in male mice. OF1 male mice were subjected to a stress period lasting 18 days. During that time, non-stressed animals were housed in groups. The cluster analysis of the behavioral profile displayed during the first social interaction divided subjects into two groups: active/aggressive (AA) and passive/reactive (PR). The day after the end of the stress period, the following behavioral analyses were performed: the sucrose preference test (SPT) on day 19, the open field test (OFT) on day 20, and the forced swim test (FST) on day 21. Immediately after completing the last test, animals were weighed, and blood samples were obtained. Then, they were sacrificed, and their prefrontal cortices and hippocampi were removed and stored to analyze monoamine levels. Stressed animals displayed anhedonia, and solely the PR mice continued to show higher levels of immobility in the OFT and FST. All stressed animals, regardless of the coping strategy, presented higher plasma corticosterone levels. In addition, stressed mice showed lower levels of tyrosine, dopamine, DOPAC, MHPG, kynurenine, kynurenic acid, and 5-HIAA levels but higher serotonin levels in the prefrontal cortex, not in the hippocampus. In conclusion, our results show that CSD induces differences in monoamine levels between brain areas, and these differences did not respond to the coping strategy adopted.

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.