DIFFERENTIAL EFFECT OF TCDD ON BRAIN-SEROTONIN METABOLISM IN A TCDD-SUSCEPTIBLE AND A TCDD-RESISTANT RAT STRAIN

Two rat strains differ widely (over 300-fold) in their LD50-values for TCDD. We have compared the effects of TCDD on brain aminergic systems in the two rat strains to assess the role of these systems in the str ain difference. Rats of both strains were given 50 mug/kg TCDD (LD100 for Long-Evans [L-E] rats; nonlethal to Han/Wistar [H/W] rats) or vehi cle. Monoamines were measured 4 or 10 days after the exposure. The was ting syndrome appeared only in L-E rats after TCDD administration. Fou r and 10 days after exposure, only L-E rats exhibited ca. 30 - 50 % el evated levels of the serotonin (5-HT) precursor tryptophan and a 5-HT metabolite 5-HIAA implying enhanced serotonergic activity by TCDD. Imp ortantly, food-restricted L-E rats, the resistant H/W rats or H/W rats subjected to TCDD exposure combined with food restriction did not exh ibit elevated tryptophan or 5-HIAA concentrations. The turnover of nor adrenaline or dopamine was not markedly affected in either rat strain by TCDD. These findings imply that the enhanced central 5-HT turnover in L-E rats may be associated with the wasting syndrome and acute leth ality of TCDD.