On the basis of the findings that the rapid influx of extracellular Zn²⁺ into nigral dopaminergic neurons causes dopaminergic neurodegeneration, here we report that AMPA causes movement disorder in rats. AMPA markedly increased turning behavior in response to apomorphine 1 and 2 weeks after AMPA injection into the substantia nigra pars compacta (SNpc), while AMPA-induced movement disorder was suppressed by co-injection of intracellular Zn²⁺ chelators, i.e., ZnAF-2DA and TPEN, suggesting that AMPA-induced movement disorder is due to intracellular Zn²⁺ dysregulation. Furthermore, AMPA markedly induced loss of nigrostriatal dopaminergic neurons 2 weeks after AMPA injection into the SNpc, while AMPA-induced neurodegeneration was also suppressed in the SNpc and the striatum by co-injection of ZnAF-2DA and TPEN. AMPA rapidly increased nigral intracellular Zn²⁺ after AMPA injection into the SNpc and this increase was blocked by co-injection of TPEN. These results indicate that AMPA receptor activation rapidly increases influx of extracellular Zn²⁺ into nigral dopaminergic neurons and causes nigrostriatal dopaminergic neurodegeneration, resulting in movement disorder in rats. The evidence that AMPA-induced intracellular Zn²⁺ dysregulation causes movement disorder via nigrostriatal dopaminergic neurodegeneration suggests that AMPA receptors, probably Ca²⁺- and Zn²⁺-permeable GluR2-lacking AMPA receptors are potential targets for overcoming Parkinson's syndrome.

基于胞外Zn ²⁺迅速流入黑质多巴胺能神经元引起多巴胺能神经退行性改变的发现，在此我们报道AMPA引起大鼠运动障碍。AMPA注射入黑质致密部（SNpc）后1和2周，AMPA显着增加了对阿扑吗啡的转向行为，而共注射胞内Zn ²⁺螯合剂ZnAF-2DA可抑制AMPA诱导的运动障碍和TPEN，表明AMPA引起的运动障碍是由于细胞内Zn ²⁺失调。此外，AMPA注射到SNpc中2周后，AMPA明显诱导了黑质纹状体多巴胺能神经元的损失，而同时注射ZnAF-2DA和TPEN，也抑制了SNpc和纹状体中AMPA诱导的神经变性。在将AMPA注射到SNpc中后，AMPA迅速增加了黑色素细胞内的Zn ²⁺，并且通过共注射TPEN阻止了这种增加。这些结果表明，AMPA受体激活迅速增加了细胞外Zn ²⁺向黑质多巴胺能神经元的流入并引起黑纹状体多巴胺能神经变性，从而导致大鼠运动障碍。AMPA诱导的细胞内Zn ²⁺的证据机能失调通过黑质纹状体多巴胺能神经退行性变引起运动障碍，表明AMPA受体，可能是缺乏Ca ²⁺和Zn ^2+的GluR2渗透性AMPA受体，是克服帕金森氏症的潜在目标。