Stahl B U, Alper R H, Rozman K
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Toxicol Lett. 1991 Dec;59(1-3):65-72. doi: 10.1016/0378-4274(91)90056-c.
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.
我们之前报道了一系列在2,3,7,8-四氯二苯并对二恶英（TCDD）中毒大鼠体内发生的生物学事件，这些事件导致大脑血清素（5-羟色胺，5-HT）水平升高，为这些动物的急性毒性（采食量减少和死亡）提供了一种可能的解释。因此，我们推测中枢5-HT储备的耗尽应该会改变TCDD诱导的饥饿综合征。通过脑室内注入神经毒素5,7-二羟基色胺（5,7-DHT）选择性地耗尽大脑5-HT。随后给这些动物给予致死剂量的TCDD。与对照动物相比，用5,7-DHT处理的大鼠下丘脑5-HT耗尽高达90%，然而TCDD仍诱导了预期的体重减轻和采食量减少。这些结果表明，虽然TCDD由于血浆色氨酸增加而导致中枢5-HT水平升高，但这可能不是这些动物采食量减少和致死的主要原因。
