Serotoninergic Mechanisms of Immunomodulation Under Different Psychoemotional States: I. A role of 5-HT_1aReceptor Subtype

Abstract

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.

Effects of Activation and Blockade of Serotonin 5-HT1A Receptors on the Immune Response in Rats Selected for Different Levels of Aggressiveness

“…As noted above, the 5-HTergic system provides an inhibitory mechanism of immunomodulation, which is mediated via 5-HT receptors including the 5-HT 1A type [12] [29] [30] [44]. In our experiments, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression that is mainly dependent on stimulation of postsynaptic 5-HT 1A receptors.…”

“…once at a dose of 1.0 mg/kg 30 min prior to immunization. The doses, timing and administration routes of drugs were based on the data of other authors [27] and on those used in our previous studies [29]. Control groups of rats received an equivalent volume of corresponding vehicle for the same period of time.…”

Contribution of brain dopamine, serotonin and opioid receptors in the mechanisms of neuroimmunomodulation: Evidence from pharmacological analysis

“…Furthermore, 5-HT 1A -and 5-HT 2A -receptors localized in the brain structures have been found to be implicated in neuroimmunomodulation [17,23,[77][78][79]. Application of a highly selective agonist of 5-HT 1A -receptors (+)-8-hydroxy-2-(di-N-propyl-amino) tetralin (8-OH-DPAT), named by some authors a "gold standard" for studying the functional activity of 5-HT 1A -receptors, at a dose activating central postsynaptic 5-HT 1A -receptors [69,80,81], led to a decrease in the number of spleen IgM-AFC in mice of different strains and in Wistar rats [78] immunized with SRBC (Table 2).…”

“…Application of a highly selective agonist of 5-HT 1A -receptors (+)-8-hydroxy-2-(di-N-propyl-amino) tetralin (8-OH-DPAT), named by some authors a "gold standard" for studying the functional activity of 5-HT 1A -receptors, at a dose activating central postsynaptic 5-HT 1A -receptors [69,80,81], led to a decrease in the number of spleen IgM-AFC in mice of different strains and in Wistar rats [78] immunized with SRBC (Table 2). This effect was dependent on the All drugs were injected intraperitoneally.…”

“…schedule of drug administration [23,78] as well as psychoemotional state of animals [78,82,83]. Immunosuppressive effect of 8-OH-DPAT was completely antagonized by pretreatment of animals with a strong 5-HT 1A -receptor antagonist [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride] (WAY-1006 35) [78], which in high doses is known to block postsynaptic 5-HT 1A -receptors and to compete with the agonist for the same binding site on the receptor [81].…”