MODULATION OF TCDD-INDUCED WASTING SYNDROME BY PORTACAVAL ANASTOMOSISAND VAGOTOMY IN LONG-EVANS AND HAN WISTAR RATS/

Portocaval anastomosis and vagotomy operations were performed in Long- Evans (L-E) and Han/Wistar (H/W) rats to elucidate the mechanism of an orexia induced by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). TCDD-sen sitive L-E rats were given a sublethal (5 mu g/kg) or a lethal dose (2 0 mu g/kg) by gavage 5-8 weeks after portocaval anastomosis. TCDD-resi stant H/W rats were given a nonlethal dose (500 or 7200 mu g/kg). The shunt operation did not reduce lethality from TCDD. The effect on wast ing of the marginally toxic dose of 5 mu g/kg in L-E rats was potentia ted by the portocaval operation, and the lethal dose was effective in both shunted and sham-operated L-E rats. TCDD failed to decrease food intake and body weight in shunted rats of H/W strain at either dose le vel though it did so in sham-operated controls. The lack of effect may be due to the already reduced weight of shunted rats at the time of T CDD dosing. TCDD anorexia was not explained by changes in histamine or serotonin (5-HT) turnover in the brain. Vagotomy did not influence le thality after TCDD, although reduction in food intake was somewhat blu nted in H/W rats. The results seem to indicate that the anorectic effe ct of TCDD is modified when portal blood bypasses the liver. The mecha nisms remain to be elucidated in detail, but the results do not favor the role of liver as the only or the major initiator of TCDD anorexia. Little evidence was found to support a crucial role of vagal afferent input.