DeHaven D L, Krigman M R, Mailman R B
Neurobehav Toxicol Teratol. 1986 Sep-Oct;8(5):475-9.
Previous studies have demonstrated that at day 7 following treatment, administration of 3 or 7 mg/kg trimethyltin (TMT) to male Long-Evans rats caused decreases in the concentrations of DA in nucleus accumbens, and perturbed serotonergic function in regions of brain that receive serotonergic innervation from the raphe nuclei. The present series of experiments extended these observations by examining the time course of these events from 14 to 28 days after treatment. Following a dose of 7 mg/kg, changes in serotonergic function, as evidenced by increased turnover and decreased concentrations of 5-HT, were present in striatum, olfactory tubercle, septum and frontal cortex. In nucleus accumbens, concentrations of DA were decreased up to 21 days, while in frontal cortex concentrations of DOPAC and HVA were elevated only at 14 days. In concert with our previous studies, these data indicate that administration of TMT continues to affect serotonergic systems up to 28 days, and dopaminergic systems up to 21 days after exposure, with striatum, nucleus accumbens, olfactory tubercle and septum exhibiting persistent effects due to administration of this neurotoxicant. These prolonged alterations in serotonergic function suggest that this system may play an important role in the response to intoxication with TMT.
先前的研究表明，在治疗后第7天，给雄性Long-Evans大鼠施用3或7mg/kg三甲基锡（TMT）会导致伏隔核中多巴胺（DA）浓度降低，并扰乱中缝核向其发出5-羟色胺能神经支配的脑区中的5-羟色胺能功能。本系列实验通过检查治疗后14至28天这些事件的时间进程，扩展了这些观察结果。在给予7mg/kg剂量后，纹状体、嗅结节、隔区和额叶皮质中出现了5-羟色胺能功能的变化，表现为5-羟色胺（5-HT）周转率增加和浓度降低。在伏隔核中，DA浓度在长达21天的时间内降低，而在额叶皮质中，3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的浓度仅在第14天升高。与我们之前的研究一致，这些数据表明，施用TMT在暴露后长达28天会持续影响5-羟色胺能系统，长达21天会影响多巴胺能系统，纹状体、伏隔核、嗅结节和隔区由于施用这种神经毒物而表现出持续的影响。5-羟色胺能功能的这些长期改变表明，该系统可能在对TMT中毒的反应中起重要作用。
