2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent known anorexigens
with an unestablished mechanism of action. In the present 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 antiemetic drug intervention (trimethobenzamine, metoclopramide) approaches. Moreover,
both the most TCDD-susceptible (Long-Evans [L-E]; IP LD50 approximately 10 micrograms/kg)
and the most TCDD-resistant (Han/Wistar [H/W]; IP LD50 > 3000 micrograms/kg) rat strains
were employed in the experiments. L-E rats were exposed to a lethal dose of TCDD (50
micrograms/kg), whereas H/W rats were treated with high but nonlethal doses (50 or
1000 micrograms/kg). TCDD produced a positive CTA response in H/W rats alone. These
animals also increased their kaolin consumption more than L-E rats of either gender
after TCDD exposure. TCDD decreased the proportional intake of energy from high-protein
diet in female L-E rats, but tended to increase it in male L-E and H/W rats. TCDD
did not affect plasma oxytocin concentration by itself, but potentiated the elevation
caused by the positive control compound, LiCl, in L-E rats on day 8. Neither antiemetic
tested had any detectable influence on TCDD-induced wasting. These findings imply
that the degree of nausea elicited by TCDD in the rat depends on strain and gender.
However, nausea has only a minor, if at all, causal role in the lethal wasting syndrome
characteristic of this compound.