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.

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent anorexigens 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 tissues after TCDD administration to adult male Long-Evans rats. Rats were given a single lethal dose of TCDD (1000 micrograms/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 analyzed for concentrations of biogenic amines and their metabolites by HPLC-EC. Administration of TCDD increased the concentration of tryptophan at 8 days after exposure by about 20% in almost all nuclei examined, with the change reaching statistical significance in the lateral hypothalamic 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 dopamine, serotonin and/or 5-hydroxyindoleacetic acid levels in most brain sites during the first day postexposure. The present results argue against a crucial role for catecholamines as mediators of TCDD toxicity. However, the delayed changes in brain tryptophan do not appear to be secondary to TCDD hypophagia.