Department of Psychology, California State University, San Bernardino, California 92407, USA.
Synapse. 2011 Apr;65(4):339-50. doi: 10.1002/syn.20852. Epub 2010 Oct 8.
The goal of the present investigation was to determine the persistence of striatal (DA) dopaminergic dysfunction after a mild chemically induced hypoxic event in Fisher 344 rats. To this end, we gave a single injection of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP; 16.5 mg/kg, i.p.) to 2-month old male F344 rats and measured various indices of striatal DA functioning and lipid peroxidation over a 3-month span. Separate groups of rats were used to measure rod walking, evoked DA release, DA content, malondialdehyde (MDA) accumulation, DA receptor binding, and tyrosine hydroxylase (TH) activity. The results showed that 3-NP exposure reduced most measures of DA functioning including motoric ability, DA release, and D(2) receptor densities for 1 to 3 months postdrug administration. Interestingly, DA content was reduced 1 week after 3-NP exposure, but rose to 147% of control values 1 month after 3-NP treatment. MDA accumulation, a measure of lipid peroxidation activity, was increased 24 h and 1 month after 3-NP treatment. 3-NP did not affect TH activity, suggesting that alterations in DA functioning were not the result of nigrostriatal terminal loss. These data demonstrate that a brief mild hypoxic episode caused by 3-NP exposure has long-term detrimental effects on the functioning of the nigrostriatal DA system.
本研究旨在确定在 Fisher 344 大鼠中轻度化学诱导缺氧事件后纹状体（DA）多巴胺能功能的持续时间。为此，我们给 2 个月大的雄性 F344 大鼠单次注射线粒体复合物 II 抑制剂 3-硝基丙酸（3-NP；16.5mg/kg，ip），并在 3 个月的时间内测量纹状体 DA 功能和脂质过氧化的各种指标。用单独的大鼠组测量棒状行走、诱发的 DA 释放、DA 含量、丙二醛（MDA）积累、DA 受体结合和酪氨酸羟化酶（TH）活性。结果表明，3-NP 暴露降低了包括运动能力、DA 释放和 D2 受体密度在内的大多数 DA 功能指标，在药物给药后 1 至 3 个月内。有趣的是，3-NP 暴露后 1 周 DA 含量降低，但 1 个月后上升至对照值的 147%。MDA 积累，一种脂质过氧化活性的测量，在 3-NP 处理后 24 小时和 1 个月增加。3-NP 不影响 TH 活性，表明 DA 功能的改变不是黑质纹状体末端丧失的结果。这些数据表明，3-NP 暴露引起的短暂轻度缺氧发作对黑质纹状体 DA 系统的功能有长期的不利影响。
