Role of central 5-HT(2) receptors in fluoxetine-induced decreases in T lymphocyte activity.
Previous studies have demonstrated that fluoxetine administration decreases mitogen-induced T lymphocyte proliferation. The present studies were carried out to determine which receptor subtype(s) was involved and whether these effects on lymphocyte responses were centrally or peripherally mediated. Two hours following administration of the 5-HT(1A) agonist 8-OH-DPAT (1 mg/kg), there was no change in lymphocyte proliferation responses, whereas the 5-HT(2) agonist DOI (2.5 mg/kg) significantly decreased (80%) proliferation. Similarly, pretreatment with the 5-HT(2) antagonists ritanserin (5 mg/kg, 30 min) or ketanserin (5 mg/kg, 1 h) was found to completely antagonize the effects of fluoxetine on lymphocyte proliferation. Consistent with central 5-HT(2) receptor involvement, microinjection of DOI (50 microg) resulted in a decrease in lymphocyte proliferation similar to that observed following systemic administration. Furthermore, central administration of ketanserin (20 microg) prevented the suppressive effects of systemic fluoxetine. Collectively, these results suggest that decreases in mitogen-induced lymphocyte proliferation following acute fluoxetine administration was due to indirect effects of fluoxetine following the activation of central 5-HT(2) receptors.
Pellegrino
Trisha C
TC
Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road, Washington, DC 20007, USA.
Bayer
Barbara M
BM
D000818:Animals; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D007267:Injections; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
D005473:Fluoxetine; D007650:Ketanserin; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D016713:Ritanserin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors