Experiments on CBA mice showed that selective stimulation of 2A serotonin receptors with DOI agonist (1 mg/kg) led to suppression of the immune response and reduction of the spleen and peripheral blood CD8(+)T cell counts with the cytotoxic/suppressor function. Selective blockade of these receptors with ketanserin (1 mg/kg) had an opposite effect: immunostimulation with an increase in CD8(+)T cell count in the spleen. These data indicate the involvement of 2A serotonin receptors in immunosuppressive mechanisms of serotoninergic system.

The present study demonstrates the involvement of serotonin (5-HT) receptors of the 5-HT 1A type in immunoinhibitory effect of 5-HTergic system of the brain. A selective agonist of 5-HT 1A receptors 8-OH-DPAT (1 mg/kg) induces the immunosuppression, whereas 5-HT 1A blockade with WAY-100635 (1 mg/kg) resulted in immunostimulation. It is also shown that immunomodulating effects of the drugs were dependent on psychoemotional status of animals acquired aggressive or submissive behavior under social conflict conditions. Activation of 5-HT 1A receptors produced a decrease of the immunity in aggressive mice, whereas 5-HT 1A receptor blockade caused immunostimulation in submissive animals.

Experiments performed on male CBA mice immunized with sheep erythrocytes at a dose of 5 x 10(8) cells showed that the selective agonist of serotonin 5-HT(1A) receptors 8-OH-DPAT (1 mg/kg) suppresses the immune response in aggressive animals. In mice demonstrating the submissive type of behavior, formed during 10 days of experience of defeats, activation of 5-HT(1A) receptors with 8-OH-DPAT had no effect on the immune response. However, treatment with the selective 5-HT(1A) receptor blocker WAY-100635 stimulated the immune response, but only in submissive mice. These data lead to the conclusion that activation and blockade of 5-HT(1A) receptors have different effects on the immune response in CBA mice depending on the initial emotional state of the animals, due to different activities of neurotransmitter systems, particularly the serotoninergic, in aggressive and submissive mice.

The development of an immune reaction in CBA mice during activation and blockade of serotonin 1A (5-HT(1A)) autoreceptors with highly selective agents has characteristic features depending on the behavioral stereotype formed. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.1 mg/kg 15 min before immunization) did not alter the number of IgM antibody-forming cells in the spleen at the peak of the immune reaction (day 4) in aggressive mice, but increased the number in submissive mice, in which the immune response without treatment was lower than that in aggressive animals. Blockade of the same receptor type with WAY-100635 (0.1 mg/kg 30 min before immunization) led to a decrease in the immune response in animals with aggressive behavior and an increase in submissive animals. The question of the influences of agents acting on presynaptic 5-HT(1A) somatodendritic autoreceptors on the immune response, depending on the functional state of 5-HT(1A) receptors and the balance of activities in the serotoninergic and dopaminergic systems as a whole, is discussed.