CHARACTERIZATION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN-INDUCED BRAIN-SEROTONIN METABOLISM IN THE RAT

It has previously been shown that a lethal dose of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) increases the brain concentrations of serotoni n precursor, tryptophan, and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in TCDD-susceptible Long-Evans but not in TCDD-resistant Han /Wistar rats. In the present study, TCDD (50 mu g/kg; LD(100) for Long -Evans and nonlethal for Han/Wistar rats) enhanced de novo biosynthesi s of serotonin in the brain of Long-Evans but not Han/Wistar or food-r estricted Long-Evans rats 10 days after exposure. Furthermore, TCDD in creased the plasma level of free tryptophan in Long-Evans rats alone, which may be causally related to the observed effects of TCDD on brain tryptophan levels. Administration of hemin modified the time course o f TCDD-induced anorexia although 10 day cumulative food consumption wa s not altered. Hemin tended to attenuate TCDD-elicited increases in br ain serotonin turnover, whereas a beta-adrenergic blocker, propranolol , did not. In the majority of Long-Evans rats, TCDD inhibited the main tryptophan degrading enzyme in the liver, tryptophan pyrrolase, but t he rest exhibited augmented activities; these effects were not altered by hemin. TCDD increased the plasma levels of nonesterified fatty aci ds in Long-Evans (five-fold) but not in Han/Wistar rats. A slight elev ation (two-fold) was also seen in food-restricted Long-Evans rats. It is concluded that TCDD selectively promotes brain serotonin turnover i n Long-Evans rats and this acceleration is related to increased plasma levels of free tryptophan. The inhibition of tryptophan catabolism in the liver and elevation of plasma nonesterified fatty acids may contr ibute to these changes.