TCDD-INDUCED HYPOPHAGIA IS NOT EXPLAINED BY NAUSEA

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent k nown anorexigens with an unestablished mechanism of action. In the pre sent study, the role of nausea in TCDD-induced hypophagia was assessed by a battery of behavioral (conditioned taste aversion [CTA], kaolin consumption, protein selection), biochemical (plasma oxytocin), and an tiemetic drug intervention (trimethobenzamine, metoclopramide) approac hes. Moreover, both the most TCDD-susceptible (Long-Evans [L-E]; IP LD 50 similar to 10 mu g/kg) and the most TCDD-resistant (Han/Wistar [H/W ]; IP LD50 >3000 mu g/kg) rat strains were employed in the experiments . L-E rats were exposed to a lethal dose of TCDD (50 mu g/kg), whereas H/W rats were treated with high but nonlethal doses (50 or 1000 mu g/ kg). TCDD produced a positive CTA response in H/W rats alone. These an imals also increased their kaolin consumption more than L-E rats of ei ther gender after TCDD exposure. TCDD decreased the proportional intak e of energy from high-protein diet in female L-E rats, but tended to i ncrease it in male L-E and H/W rats. TCDD did not affect plasma oxytoc in concentration by itself, but potentiated the elevation caused by th e positive control compound, LiCl, in L-E rats on day 8. Neither antie metic tested had any detectable influence on TCDD-induced wasting. The se findings imply that the degree of nausea elicited by TCDD in the ra t depends on strain and gender. However, nausea has only a minor, if a t all, causal role the lethal wasting syndrome characteristic of this compound.