T Matitaishvili, T Domianidze, G Burjanadze, M Shengelia, N Menteshashvili
Prolonged social isolation constitutes a potent chronic stressor capable of inducing behavioral and neurochemical alterations associated with anxiety, depression, and cognitive dysfunction. In rodent models, dominant and submissive individuals exhibit distinct behavioral and neuroendocrine responses under conditions of social stress. The present study aimed to evaluate the effects of 30 days of social isolation on depressive-like and anxiety-like behaviors, as well as cognitive performance, in rats with differing social status. Experiments were conducted on 20 groups of white laboratory rats (200-250 g), with three male animals per group. The animals were assigned to either control or experimental conditions. Social status within each group was determined using food- and water-motivation conflict paradigms. Rats in the experimental groups were subjected to 30 days of individual housing (social isolation), whereas control animals were maintained under standard group-housing conditions. Behavioral assessments included the forced swim test and the elevated plus maze. Short-term spatial memory was evaluated using the Y-maze spontaneous alternation task. Serotonin concentrations in the hypothalamus and hippocampus were quantified using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using two-way ANOVA followed by Tukey's HSD post hoc test. Under control conditions, submissive rats displayed higher immobility in the forced swim test and lower basal hypothalamic serotonin levels compared to dominant rats, whereas anxiety indices and short-term memory performance did not differ significantly. Chronic social isolation significantly increased immobility time and reduced the time spent in the open arms of the elevated plus maze in both dominant and submissive rats, indicating enhanced depressive- and anxiety-like behaviors. Anxiety-like responses were more pronounced in submissive rats. Isolation also impaired short-term spatial memory in both dominant and submissive animals, as reflected by a reduced spontaneous alternation ratio in the Y-maze. Neurochemically, hippocampal serotonin levels were significantly decreased in both social groups following isolation. In contrast, hypothalamic serotonin levels increased only in submissive rats, suggesting a social status-dependent neuroendocrine adaptation. Overall, long-term social isolation induces marked behavioral and region-specific serotonergic alterations irrespective of social status; however, submissive animals demonstrate greater anxiety-related vulnerability and distinct hypothalamic serotonergic upregulation. These findings highlight the modulatory role of social status in stress susceptibility and suggest that region-specific serotonergic imbalance may represent a neurobiological mechanism underlying differential vulnerability to chronic social stress. The results underscore the importance of considering individual social profiles in future research on stress adaptation mechanisms and stress-induced psychopathologies.