In Vivo Electrochemical Studies of Dopamine Overflow and Clearance in the Striatum of Normal and MPTP‐Treated Rhesus Monkeys
In Vivo Electrochemical Studies of Dopamine Overflow and Clearance in the Striatum of Normal and MPTP‐Treated Rhesus Monkeys
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DOI：
10.1046/j.1471-4159.1996.66020579.x
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发表时间：
1996-02
影响因子：
4.7
通讯作者：
Greg A. Gerhardt;W. Cass;John L. Hudson;Michael A. Henson;Zhiming Zhang;Aliza Ovadia;B. Hoffer;D. Gash
中科院分区：
文献类型：
--
作者：
Greg A. Gerhardt;W. Cass;John L. Hudson;Michael A. Henson;Zhiming Zhang;Aliza Ovadia;B. Hoffer;D. Gash
摘要：采用Nafion涂层碳纤维电极（30-90µm o.d），采用快速时间电流记录技术，研究了正常和1‐甲基‐4‐苯基‐1,2,3,6‐四氢吡啶（MPTP）处理的恒河猴纹状体中多巴胺（DA）的溢出和摄取情况。猴子被异氟醚麻醉并放置在立体定向装置中。使用磁共振成像引导的无菌立体定向程序植入电化学电极，并使用单桶微移液管局部施用钾或DA。钾诱发了大量的DA样电化学信号向未损伤或正常的恒河猴壳核和尾状核的脑细胞外空间溢出。相反，在MPTP损伤的纹状体中，钾没有产生任何可检测到的DA变化（约97%耗竭）。此外，与未损伤纹状体相比，局部应用DA在损伤尾状核和壳核中的扩散/清除明显改变。MPTP治疗的猴子中残余酪氨酸羟化酶阳性神经元的细胞计数，结合DA及其代谢物的全组织水平，表明MPTP病变对黑质纹状体DA系统产生了广泛的损伤。这些数据表明，MPTP病变后残留的多巴胺能纤维功能失调，并大大降低了高亲和力DA摄取的能力。
Abstract: Rapid chronoamperometric recordings, using Nafion‐coated carbon‐fiber electrodes (30–90 µm o.d.), were used to investigate overflow and uptake of dopamine (DA) in the striatum of normal and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated rhesus monkeys. The monkeys were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging‐guided sterile stereotaxic procedures were used for implantations of the electrochemical electrodes coupled with single‐barrel micropipettes that were used to apply potassium or DA locally. Potassium evoked a robust overflow of DA‐like electrochemical signals into the brain extracellular space in the unlesioned or normal putamen and caudate nucleus of the rhesus monkeys. In contrast, potassium did not produce any detectable changes (> 97% depletion) of DA in the MPTP‐lesioned striatum. In addition, the diffusion/clearance of locally applied DA was markedly altered in the lesioned caudate nucleus and putamen compared with unlesioned striatum. Cell counts of the number of residual tyrosine hydroxylase‐positive neurons in MPTP‐treated monkeys, in conjunction with whole‐tissue levels of DA and its metabolites, showed that the MPTP lesions produced extensive damage of the nigrostriatal DA system. These data indicate that residual dopaminergic fibers remaining after MPTP lesions are dysfunctional and have a greatly diminished capacity for high‐affinity DA uptake.