Effects of a primary immune response to T-cell dependent antigen on serotonin metabolism in frontal cortex: in vivo microdialysis study in freely 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 of the neurotransmitter at nerve terminals. In the present study, we first investigated the changes of central serotonin (5-HT) metabolism in Fischer 344 male rats at 2, 3, 4 and 5 days following i.v. immunization with sheep red blood cell (SRBC). Major decreases in 5-HT levels were evident in the hypothalamus (Hy) and cortex (Cx) at a time which corresponded to the late phase of the production of specific antibodies to SRBC measured with a plaque-forming cell assay (PFC). A pretreatment with an immunosuppressive drug, cyclosporin A (CsA; 12.5 mg/kg by gavage for 7 days) prevented the decreases in cortical 5-HT levels. Concomitantly, a 2-fold increase in the basal 5-HT release at frontocortical nerve terminals was observed by using in vivo microdialysis in awake rats on Day 3 following SRBC inoculation. This effect was totally suppressed by CsA. Our data suggest that the decrease in brain 5-HT levels that occurs after antigen administration may reflect a specific short-lasting CsA-dependent-release of 5-HT at frontocortical nerve terminals at a time (Day 3 or 4) when the splenic immune response is maximal.
Gardier
A M
AM
Department of Pharmacology JE 92-372 DRED, CJF INSERM 93.01, Chatenay-Malabry, France.
Kachaner
S
S
Kahn Shaghaghi
E
E
Blot
C
C
Bohuon
C
C
Jacquot
C
C
Pallardy
M J
MJ
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D017707:Erythrocyte Transfusion; D005625:Frontal Lobe / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009043:Motor Activity; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism*; D012756:Sheep / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D016572:Cyclosporine; D011188:Potassium