A salient sign of fatal
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) intoxication is dramatic
body weight loss accompanied by hypophagia. Yet, the nature of this
wasting syndrome is unknown. As all of the current leptogenic (weight reducing) drugs exert their action by affecting aminergic neurotransmission, this study set out to screen the reversibility of
TCDD-induced
anorexia with the following agents modulating aminergic neurotransmission:
amphetamine,
amperozide,
chlordiazepoxide,
clonidine,
haloperidol,
morphine, PCPA,
phenoxybenzamine,
reserpine and
sotalol. In addition,
dexamethasone,
indomethacin, and
insulin were included in the
drug battery. The agents were administered subcutaneously to adult male Long-Evans rats over a period lasting from 3 to 14 days. Half of each
drug group was concomitantly exposed to a lethal dose of
TCDD (20 micrograms/kg). None of the regimens were able to mitigate the
wasting syndrome.
TCDD proved to markedly diminish the nocturnal feed intake while practically sparing daytime feed consumption.
Insulin increased the daytime feeding of
TCDD-exposed rats, and the termination of treatment resulted in almost total aphagia in this group.
Amphetamine,
dexamethasone, PCPA, and
reserpine caused
weight loss in drug control rats and aggravated the action of
TCDD. However,
clonidine had no effect on the weight of control rats but accelerated weight decline in
TCDD-cotreated animals.
TCDD seemed to have a somewhat minor influence on drinking than on feeding.
Clonidine stimulated water intake in controls but not in
TCDD-exposed rats. These results suggest that aminergic neurotransmission is not specifically or crucially affected by
TCDD, but further studies are needed to confirm this conclusion.