Stahl B U, Rozman K
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Toxicol Appl Pharmacol. 1990 Oct;106(1):158-62. doi: 10.1016/0041-008x(90)90116-c.
The most striking sign of acute toxicity of TCDD in animals is a progressive reduction of feed intake, accompanied by loss of body weight eventually resulting in death. The mechanism(s) of this voluntary feed refusal is (are) not known but it is generally accepted that both centrally and peripherally (via feedback) acting anorectic agents exert their effect(s) in the hypothalamus. In this study direct administration into the lateral cerebral ventricle of rats resulted in much higher concentrations of TCDD in the hypothalamus and also in other regions of the brain than after a lethal intravenous (iv) injection. While rats injected iv displayed the expected cachectic syndrome, intracerebroventricularly (icv)-dosed animals ate and gained weight normally. These findings preclude the possibility of a direct effect of TCDD on appetite-regulating areas of the brain. Moreover, these results require the assumption that the appetite suppressive effect of TCDD is due to a (feedback) mechanism originating in the periphery.
2,3,7,8-四氯二苯并对二恶英（TCDD）对动物的急性毒性最显著的迹象是采食量逐渐减少，并伴有体重减轻，最终导致死亡。这种自主拒食的机制尚不清楚，但人们普遍认为，中枢和外周（通过反馈）作用的食欲抑制剂在下丘脑发挥作用。在本研究中，直接向大鼠侧脑室给药后，下丘脑和大脑其他区域的TCDD浓度比致死性静脉注射后高得多。虽然静脉注射的大鼠出现了预期的恶病质综合征，但脑室内给药的动物饮食和体重正常增加。这些发现排除了TCDD对大脑食欲调节区域直接作用的可能性。此外，这些结果需要假设TCDD的食欲抑制作用是由于外周起源的（反馈）机制。
