Pranzatelli M R, Tailor P T, Pluchino R, Gonzales W, Simmens S
Department of Neurology, George Washington University, Washington, D.C.
Neurotoxicology. 1994 Summer;15(2):261-72.
An abnormality of serotonergic neurotransmission has been hypothesized in p,p'-DDT intoxication to explain myoclonus and the antimyoclonic properties of 5-hydroxytryptophan (5-HTP). To study the role of serotonin (5-HT) receptors in myoclonus induced by p,p'-DDT in the rat, we performed time-course and dose-response studies of the effects of p,p'-DDT on behavior and regional 5-HT1 and 5-HT2 binding sites. At a time when low dose (80 mg/kg) p,p'-DDT elicited stimulus-sensitive and spontaneous myoclonus, there were no significant changes in Bmax or Kd of 5-HT1A, 5-HT1B, 5-HT1C sites in cortex, striatum, brainstem or spinal cord, agonist- or antagonist-labelled 5-HT2 sites in cortex, or 5-HT uptake sites. High dose p,p'-DDT (1000 but not 500 mg/kg), which also induced convulsions, only slightly increased 5-HT1 (unsubtyped) binding sites in cortex but not in brainstem or spinal cord and had no effect on antagonist-labelled 5-HT2 sites. In naive frontal cortex in vitro, 1 microM p,p'-DDT displaced neither [3H]5-HT or [3H]ketanserin specific binding. Lesions of central indoleamine neurons made with 5,7-dihydroxytryptamine significantly prolonged the latency and attenuated the severity of p,p'-DDT behavioral abnormalities, increasing the dose of p,p'-DDT which induced myoclonus (MD50) or convulsions (CD50) in 50 percent of the rats. This is the first report of 5,7-DHT-induced attenuation in the p,p'-DDT myoclonic model.
在对p,p'-滴滴涕中毒的研究中，有人提出血清素能神经传递异常可解释肌阵挛以及5-羟色氨酸（5-HTP）的抗肌阵挛特性。为了研究血清素（5-HT）受体在大鼠p,p'-滴滴涕诱发的肌阵挛中的作用，我们进行了关于p,p'-滴滴涕对行为及脑区5-HT1和5-HT2结合位点影响的时间进程和剂量反应研究。当低剂量（80毫克/千克）p,p'-滴滴涕引发刺激敏感性和自发性肌阵挛时，皮质、纹状体、脑干或脊髓中的5-HT1A、5-HT1B、5-HT1C位点，皮质中激动剂或拮抗剂标记的5-HT2位点，以及5-HT摄取位点的Bmax或Kd均无显著变化。高剂量p,p'-滴滴涕（1000毫克/千克而非500毫克/千克），同样会诱发惊厥，仅使皮质中5-HT1（未分型）结合位点略有增加，而脑干或脊髓中无此变化，且对拮抗剂标记的5-HT2位点无影响。在体外的正常额叶皮质中，1微摩尔p,p'-滴滴涕既不取代[3H]5-HT也不取代[3H]酮色林的特异性结合。用5,7-二羟色胺造成的中枢吲哚胺神经元损伤显著延长了潜伏期，并减轻了p,p'-滴滴涕行为异常的严重程度，使半数大鼠诱发肌阵挛（MD50）或惊厥（CD50）所需的p,p'-滴滴涕剂量增加。这是关于5,7-二羟色胺在p,p'-滴滴涕肌阵挛模型中诱导作用减弱的首次报道。
