Characterization of the wasting syndrome in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Treatment of male rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a dose-dependent decrease in body weight, feed intake, resting and total oxygen consumption, and spontaneous motor activity. In animals treated with a nonlethal dose (5 or 15 micrograms/kg), feed intake and oxygen consumption recover within 3 weeks post-treatment to levels appropriate for the reduced weight of the animals. Rats treated with a lethal dose (50 micrograms/kg) lose weight continuously after treatment and typically die at a body weight approximately half that of age-matched, control rats. The similar dose and time dependencies for reduction of feed intake and weight suggest that hypophagia is the major factor responsible for weight loss in TCDD-treated rats. To determine if this hypophagia is a primary or secondary effect of TCDD treatment, rats whose body weights were reduced by food restriction prior to treatment (25 micrograms/kg) were studied. When allowed to feed ad libitum immediately after treatment, these animals exhibited relative hyperphagia and weight gain demonstrating that TCDD did not impair their capacity to feed. This finding suggests that the primary effect of TCDD is not on a system that controls feed intake, but rather on one that regulates body weight. It is proposed, as a heuristic model of the wasting syndrome, that TCDD treatment lowers a "set point" for regulated body weight in the rat in a dose-dependent fashion and that hypophagia serves, as a secondary response, to reduce the animal's weight to the lower regulation level determined by the dose administered.