Abstract
The aim of the present study was to investigate the effects of the anti-asthenic drug ladasten on behavioral patterns and T-cell subsets in blood, spleen, and thymus in socially stressed male C57Bl/6 mice. Mice subjected to social defeat stress (SDS) for 25 days developed a depressive-like phenotype. The submissive SDS animals were assigned to one of two treatment groups: one group was treated with ladasten (30 mg/kg, i.p.) for up to 5 days, and the other one was administered vehicle as a control. Twenty four hours after the last injection, behavioral parameters were tested, and trunk blood and tissue samples were collected. SDS mice from the vehicle-treated group showed a subordinate and passive avoidance behavior with significantly decreased spontaneous locomotor activity (SLA) and exhibited impaired parameters in the forced swimming test (FST). Changes in behavioral status were correlated with an increase spleen weight, a decrease in thymic index and a shift in the CD4/CD8 balance toward T-cytotoxic cells. The behavior parameters were reversed in the group treated with ladasten compared to the untreated SDS group and were similar to those of unstressed mice. Treatment of socially stressed mice with ladasten normalized the amount of T-lymphocyte cells in the blood, spleen, and thymus. These findings support the notion that depression is accompanied by cell-mediated immune activation and that targeting this pathway may be a new therapeutic approach for treatment. Furthermore, our data support further investigations of ladasten as a potent anti-depressive drug which can be used alone as well as in combination with other anti-depressants.
Highlights
An enlarging body of evidence suggests the presence of interactions among the immune system, the central nervous system and the endocrine system, where these systems can be influenced by physiological and social factors [1]
Our data are consistent with previous studies which have demonstrated that social defeat stress in mice after repeated experiences of aggression results in profound behavioral changes reminiscent of chronic stress disorder and major depression [28-30]
Earlier findings completely align with our results, showing a decrease in the population of T cells in primary and secondary immune organs and a stress-induced shift in the CD4+/CD8+ ratio toward T-cytotoxic subsets associated with the development of depression in mice exposed to social defeat stress (SDS) [31,35]
Summary
An enlarging body of evidence suggests the presence of interactions among the immune system, the central nervous system and the endocrine system, where these systems can be influenced by physiological and social factors [1]. Based on evidence, including the findings of clinical depression studies and animal models, the new “5-HT” (serotonin) hypothesis of depression, which states that the T cell-mediated immune (CMI) activation con-. The long-term activation of CMI contributes to depressive symptoms and is accompanied by a Th-1-like shift away from Th-2 and Th-3-like cells, leading to the development of immune deficiency [2,5]. Effects of the Novel Anti-Asthenic Drug Ladasten on Behavior and T-Cell Subsets Alterations in a Social Defeat Animal Model of Depression that dopamine might play a role in depression and the action of antidepressants. It was postulated that depression was due to an imbalance and to decrease in extracellular dopamine levels [8]
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