Rozman K, Pfeifer B, Kerecsen L, Alper R H
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Arch Toxicol. 1991;65(2):124-8. doi: 10.1007/BF02034938.
The major cause of TCDD-induced death in rats is a progressive voluntary feed refusal which has been correlated with reduced gluconeogenesis. Since centrally administered TCDD does not cause death or decreased feed intake in rats, the ability of TCDD to suppress appetite via peripheral mechanisms acting on the central nervous system was examined in two experimental models. First, it was found that the feed intake of rats on scheduled feeding cycles was not decreased by blood transfused from rats with TCDD-induced appetite suppression (8 days after a lethal dose of TCDD, i.p.). In contrast, a similar transfusion from normal, satiated rats did reduce feed intake of recipient rats by approximately 40%, suggesting that TCDD-treated rats are not satiated but rather that they are not hungry. In the second study tryptophan (the amino acid precursor of the neurotransmitter serotonin) was measured in the plasma and tryptophan, serotonin, norepinephrine and dopamine in the hypothalamus as well as dopamine and its metabolites in the striatum 4, 8, and 16 days after TCDD dosage (125 micrograms/kg, i.p.). Progressive time-dependent increases in tryptophan levels in plasma and brain were paralleled by increases in brain serotonin and 5-hydroxyindoleacetic acid (the primary metabolite of serotonin) in TCDD-treated rats. No changes were observed regarding the other biogenic amines. It is suggested based on these data and on substantial evidence from the published literature that a serotonergic mechanism may be involved in TCDD-induced feed intake reduction.
大鼠中2,3,7,8-四氯二苯并对二噁英（TCDD）诱导死亡的主要原因是渐进性的自愿拒食，这与糖异生减少有关。由于向大鼠中枢给予TCDD不会导致死亡或减少摄食量，因此在两个实验模型中研究了TCDD通过作用于中枢神经系统的外周机制抑制食欲的能力。首先，发现接受来自TCDD诱导食欲抑制的大鼠（腹腔注射致死剂量的TCDD 8天后）的输血后，按计划进食周期进食的大鼠的摄食量并未减少。相反，来自正常、饱腹大鼠的类似输血确实使受体大鼠的摄食量减少了约40%，这表明经TCDD处理的大鼠并非饱腹，而是不饥饿。在第二项研究中，在给予TCDD（125微克/千克，腹腔注射）后4、8和16天，测量了血浆中的色氨酸（神经递质血清素的氨基酸前体）以及下丘脑中的色氨酸、血清素、去甲肾上腺素和多巴胺，以及纹状体中的多巴胺及其代谢产物。在经TCDD处理的大鼠中，血浆和脑中色氨酸水平随时间的渐进性增加与脑中血清素和5-羟吲哚乙酸（血清素的主要代谢产物）的增加平行。未观察到其他生物胺有变化。基于这些数据以及已发表文献中的大量证据，提示血清素能机制可能参与了TCDD诱导的摄食量减少。
