Depletion of brain serotonin does not alter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced starvation syndrome in the rat.
We have previously reported a series of biological events in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-intoxicated rats which resulted in elevated brain serotonin (5-HT) levels, offering a possible explanation of the acute toxicity (reduced feed intake and death) in these animals. It was thus hypothesized that depletion of central 5-HT stores should alter the TCDD-induced starvation syndrome. Brain 5-HT was selectively depleted by intracerebroventricular infusions of the neurotoxin 5,7-dihydroxytrytamine (5,7-DHT). Subsequently the animals were given a lethal dose of TCDD. In rats treated with 5,7-DHT hypothalamic 5-HT was depleted up to 90% compared to control animals, yet TCDD induced the expected reduction of bodyweight and feed intake. These results suggest that although TCDD increases central 5-HT levels as a result of increased plasma tryptophan, this may not be the main cause for reduced feed intake and lethality in these animals.
Stahl
B U
BU
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Alper
R H
RH
Rozman
K
K
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013217:Starvation / Q000139:chemically induced
D000072317:Polychlorinated Dibenzodioxins; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin