TCDD-induced hypophagia is not explained by nausea.
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.
Pohjanvirta
R
R
National Public Health Institute, Division of Environmental Health, Kuopio, Finland.
Unkila
M
M
Tuomisto
J
J
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D007616:Kaolin; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D009325:Nausea / Q000139:chemically induced* / Q000523:psychology; D010121:Oxytocin / Q000097:blood; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013649:Taste / Q000187:drug effects
D000932:Antiemetics; D001549:Benzamides; D000072317:Polychlorinated Dibenzodioxins; D007616:Kaolin; D010121:Oxytocin; D008787:Metoclopramide; C100146:trimethobenzamide