Pu C, Fisher J E, Cappon G D, Vorhees C V
Division of Basic Science Research, Children's Hospital Research Foundation and Neuroscience Program, University of Cincinnati, OH 45229-3039.
Brain Res. 1994 Jun 27;649(1-2):217-24. doi: 10.1016/0006-8993(94)91067-7.
Administration of methamphetamine (MA) induces degeneration of dopaminergic nerve terminals and astrogliosis, such as hypertrophy and an increase in apparent number, in the neostriatum. In this experiment adult rats were treated with MA (10 mg/kg, i.p.) 4 times in one day at 2 h intervals. Amfonelic acid (AFA), a dopamine reuptake inhibitor, was administered (20 mg/kg, i.p.) at the same time the last MA dose was given. Three days later, dopaminergic terminals and astrocytes were examined immunohistochemically and the contents of striatal dopamine and its metabolites were analyzed by HPLC. The results showed that MA-induced the typical depletion of dopaminergic terminals, reduction of dopamine content and astrogliosis in the neostriatum. AFA treatment completely prevented the effects of MA on the dopaminergic system, both morphologically and biochemically. However, the reaction of astrocytes remained in the region where the most severe depletion of dopaminergic terminals was seen in MA treated animals (ventral-lateral portion of neostriatum). The results support the concept that the dopamine transporter is involved in MA-induced dopaminergic nerve terminal degeneration. The results also indicate that blocking the dopamine transporter cannot completely prevent the reaction of astrocytes in the neostriatum, which indicates that the astrocytic reaction can be induced by factors other than degeneration of dopaminergic terminals in this region. Based on these and other data, it is hypothesized that MA may cause degeneration of corticostriatal glutamate pathways and this effect may be responsible for the astrogliosis in MA-AFA treated animals.
给予甲基苯丙胺（MA）会导致新纹状体中多巴胺能神经末梢变性和星形胶质细胞增生，如肥大和表观数量增加。在本实验中，成年大鼠在一天内每隔2小时腹腔注射MA（10mg/kg）4次。在最后一次给予MA的同时腹腔注射多巴胺再摄取抑制剂安非他明酸（AFA，20mg/kg）。三天后，通过免疫组织化学检查多巴胺能末梢和星形胶质细胞，并通过高效液相色谱法分析纹状体多巴胺及其代谢产物的含量。结果表明，MA诱导新纹状体中多巴胺能末梢典型性耗竭、多巴胺含量降低和星形胶质细胞增生。AFA处理在形态学和生物化学方面完全阻止了MA对多巴胺能系统的影响。然而，在MA处理的动物中多巴胺能末梢耗竭最严重的区域（新纹状体腹外侧部分），星形胶质细胞的反应仍然存在。这些结果支持多巴胺转运体参与MA诱导的多巴胺能神经末梢变性这一观点。结果还表明，阻断多巴胺转运体不能完全阻止新纹状体中星形胶质细胞的反应，这表明该区域星形胶质细胞反应可由多巴胺能末梢变性以外的因素诱导。基于这些及其他数据，推测MA可能导致皮质纹状体谷氨酸能通路变性，这种作用可能是MA-AFA处理动物中星形胶质细胞增生的原因。
