EFFECTS OF A PRIMARY IMMUNE-RESPONSE TO T-CELL-DEPENDENT ANTIGEN ON SEROTONIN METABOLISM IN FRONTAL-CORTEX - IN-VIVO MICRODIALYSIS STUDY INFREELY MOVING FISCHER-344 RAT

Antigenic challenge is known to influence brain catecholamine turnover , e.g. hypothalamic norepinephrine activity, but little is known about effects on the activity of serotoninergic neurons, i.e. the release o f the neurotransmitter at nerve terminals. In the present study, we fi rst investigated the changes of central serotonin (5-HT) metabolism in Fischer 344 male rats at 2, 3, 4 and 5 days following i.v. immunizati on with sheep red blood cell (SRBC). Major decreases in 5-HT levels we re evident in the hypothalamus (Hy) and cortex (Cx) at a time which co rresponded to the late phase of the production of specific antibodies to SRBC measured with a plaque-forming cell assay (PFC). A pretreatmen t with an immunosuppressive drug, cyclosporin A (CsA; 12.5 mg/kg by ga vage for 7 days) prevented the decreases in cortical 5-HT levels. Conc omitantly, a 2-fold increase in the basal 5-HT release at frontocortic al nerve terminals was observed by using in vivo microdialysis in awak e rats on Day 3 following SRBC inoculation. This effect was totally su ppressed by CsA. Our data suggest that the decrease in brain 5-HT leve ls that occurs after antigen administration may reflect a specific sho rt-lasting CsA-dependent-release of 5-HT at frontocortical nerve termi nals at a time (Day 3 or 4) when the splenic immune response is maxima l.