Abstract
Serotonin 5-HT2A receptors are playing an important role in the pathophysiology of aggressive behaviors and in the control of immune function. In the present study, we analyzed the effects of activation and blockade of 5-HT2A receptors with selective ligands on the immune response formation in animals with aggressive behaviors induced by genetic factors (rats selected for the increased aggressiveness toward human) or by chronic social stress (mice of the CBA/Lac strain engaged in 10 days of social confrontations). Activation of 5-HT2A receptors with DOI at 1.0 mg/kg reduced the immune response level both in aggressive rats and mice compared to the corresponding vehicle-treated groups, while DOI administration did not alter the immune reaction in nonaggressive animals. The blockade of 5-HT2A receptors with ketanserin at 1.0 mg/kg resulted in immunostimulation both in mice of the CBA strain not subjected to social stress (the controls) and in nonaggressive rats selected for elimination of aggressiveness. On the other hand, its administration to CBA mice demonstrating offensive aggression enhanced the immune reaction, while the same dose of ketanserin did not modify the immune response level in rats with genetic predisposition to the increased defensive aggression. Thus, our data suggest that the role of 5-HT2A receptors in immunomodulation depends on the specific type of aggression that may be taking into account in the treatment of some neuropsychiatric disorders with the antipsychotic drugs and antidepressants targeting 5-HT2A receptors.
Highlights
Most of the evidence to date provides support for a key role of the serotoninergic (5-HT) system and specific receptor subtypes in the regulation of aggressive forms of behavior [1]-[6]
Rats selected for the enhanced aggressiveness toward humans showed significantly higher IgM-immune response to sheep red blood cells (SRBC) (Figure 1), that is characteristic of this genetic line [18] [28] [29]
Activation of 5-HT2A receptors with DOI at 1.0 mg/kg reduced the immune response level both in rats selected for a high level of aggressiveness and in aggressive mice engaged in social confrontations for 10 days compared to the corresponding vehicle-treated groups
Summary
Most of the evidence to date provides support for a key role of the serotoninergic (5-HT) system and specific receptor subtypes in the regulation of aggressive forms of behavior [1]-[6]. An important role of pre- and postsynaptic 5-HT1A receptors in the immune response control has been shown in normal, and in mice and rats displaying either depressive-like behavior or increased aggressiveness [14] [16] [18]-[21]. It has been reported that activation of 5-HT2A receptors, localized only postsynaptically, with their preferential agonist DOI resulted in a decrease of the rosette-forming cell numbers and cytotoxic/suppressor CD8+T lymphocytes in the spleen of mice [15], as well as in the proliferative activity of T lymphocytes in rats [13]. The main aim of the present study, was to analyze the effects of activation and blockade of 5-HT2A receptors on the immune response in rats selected for the increased aggressiveness toward human (defensive aggression) or its absence, and in aggressive mice of the CBA/Lac strain exposed to chronic stressful conditions (offensive aggression)
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