EFFECT OF A SINGLE LETHAL DOSE OF TCDD ON THE LEVELS OF MONOAMINES, THEIR METABOLITES AND TRYPTOPHAN IN DISCRETE BRAIN NUCLEI AND PERIPHERAL-TISSUES OF LONG-EVANS RATS

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent a norexigens in rats with a yet unidentified mechanism of action. Since biogenic amines are known to essentially participate in the control of body weight and food intake, their levels were determined in various hypothalamic and other brain sites together with selected peripheral t issues after TCDD administration to adult male Long-Evans rats. Rats w ere given a single lethal dose of TCDD (1000 mug/kg intraperitoneally, in dimethylsulphoxide) or vehicle alone and they were decapitated at 1, 5, 25 hr or 8 days after TCDD administration. The samples were anal yzed for concentrations of biogenic amines and their metabolites by HP LC-EC. Administration of TCDD increased the concentration of tryptopha n at 8 days after exposure by about 20% in almost all nuclei examined, with the change reaching statistical significance in the lateral hypo thalamic area and in lateral and medial accumbens nuclei. Importantly, this elevation was not seen in pair-fed control animals. Although not statistically significant, there was a tendency to 5-10% diminished d opamine, serotonin and/or 5-hydroxyindoleacetic acid levels in most br ain sites during the first day postexposure. The present results argue against a crucial role for catecholamines as mediators of TCDD toxici ty. However, the delayed changes in brain tryptophan do not appear to be secondary to TCDD hypophagia.