These findings indicate that the CMS paradigm may cause anxiety-like behavior in these socially isolated male mice. In the TST and FST, the immobility times of mice in Group II and Group III were significantly longer than in controls, which is consistent with previous reports. Interestingly, we found that isolated mice exposed to aggression by physical contact showed significantly increased immobility times in the FST, whereas the immobility times in the TST remained the same. Although the reasons underlying this difference are currently unclear, it is likely that the neurobiological pathways mediated by these two models are different. For example, quantitative trait loci analysis using C57/B6 mice identified genes that may contribute to the difference responses in immobility times between the TST and FST. This highlights the genetic contribution to the behavioral performances in these two paradigms. Nonetheless, it should be noted that isolationinduced aggressive behavior could MK-4827 increase depressive-like behavior in isolated male mice subjected to unpredictable CMS. It is well known that social isolation of male mice induces offensive aggressive behavior. A number of neurotransmitters, including serotonin, norepinephrine, dopamine, and GABA, and BDNF are thought to be involved in the is social isolation Cinduced aggression. It has been reported that early social isolation in mice induces robust changes in postsynaptic, serotonergic receptor gene transcription, motor hyperactivity and behavioral disinhibition. Furthermore, serotonergic drugs, including selective serotonin reuptake inhibitors, reverse isolation-induced aggressive behavior in male mice, suggesting a role for serotonergic neurotransmission in isolationinduced aggression in male mice. It is therefore likely that disturbances in serotonergic neurotransmission may be observed in the brain of our CMS model mice. The CMS models are considered to be of high face, construct and predictive validity. In these models, prolonged exposure to uncontrollable and unpredictable stressors results in depressive-like behavior that can be INCB18424 abmole bioscience prevented or reversed by chronic but not acute antidepressant treatment.