Frohna P A, Rothblat D S, Joyce J N, Schneider J S
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Synapse. 1995 Jan;19(1):46-55. doi: 10.1002/syn.890190107.
The administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to adult cats severely disrupts the dopaminergic innervation of the striatum. Animals display a parkinson-like syndrome, consisting of akinesia, bradykinesia, postural instability, and rigidity, which spontaneously recovers by 4-6 weeks after the last administration of MPTP. In this study we used quantitative receptor autoradiography to examine changes in DA uptake sites and DA receptors in the basal ganglia of normal, and symptomatic and recovered MPTP-treated cats. Consistent with the destruction of the nigrostriatal DA pathway, there was a severe loss of DA uptake sites, labeled with [3H]-mazindol, in the caudate nucleus (64-82%), nucleus accumbens (44%), putamen (63%), and substantia nigra pars compacta (SNc, 53%) of symptomatic cats. Following behavioral recovery, there were no significant changes in DA uptake site density. Significant increases of [3H]-SCH 23390 binding to D1 DA receptors were observed in the dorsal caudate (> 24%; P < 0.05) of symptomatic cats and in all regions of the caudate-putamen (> 30%; P < 0.05) of recovered animals. [3H]-SCH 23390 binding in the substantia nigra pars reticulata was half of that in the striatum and showed no changes in symptomatic or recovered animals. No alterations in the binding of [125I]-epidepride to D2 receptors was observed in any region of the striatum in either symptomatic or recovered animals. [125I]-Epidepride binding in the SNc was decreased by > 36% (P < 0.05) following MPTP treatment. These data show that cats made parkinsonian by MPTP exposure have a significant decrease in the number of DA reuptake sites throughout the striatum and that recovery of sensorimotor function in these animals is not correlated with an increase in the number of striatal reuptake sites. Behavioral recovery, however, does seem to be correlated with a general elevation of D1 receptors throughout the striatal complex. The present data also show that direct correlations between changes in DA receptor regulation after a large DA depleting lesion and behavioral deficits or recovery from those deficits are difficult and that the relationships between DA receptors/transporters and behavior require further study.
给成年猫注射神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）会严重破坏纹状体的多巴胺能神经支配。动物会出现类似帕金森综合征的症状，包括运动不能、运动迟缓、姿势不稳和僵硬，在最后一次注射MPTP后4 - 6周会自发恢复。在本研究中，我们使用定量受体放射自显影技术来检测正常猫、有症状的MPTP处理猫以及恢复后的MPTP处理猫基底神经节中多巴胺摄取位点和多巴胺受体的变化。与黑质纹状体多巴胺能通路的破坏一致，有症状的猫尾状核（64 - 82%）、伏隔核（44%）、壳核（63%）和黑质致密部（SNc，53%）中，用[3H]-吗茚酮标记的多巴胺摄取位点严重减少。行为恢复后，多巴胺摄取位点密度没有显著变化。在有症状的猫的背侧尾状核中观察到[3H]-SCH 23390与D1多巴胺受体的结合显著增加（> 24%；P < 0.05），在恢复后的动物的尾状核 - 壳核所有区域中也显著增加（> 30%；P < 0.05）。黑质网状部中[3H]-SCH 23390的结合是纹状体中的一半，在有症状或恢复后的动物中没有变化。在有症状或恢复后的动物的纹状体任何区域中，未观察到[125I]-表螺环哌啶与D2受体结合的改变。MPTP处理后，SNc中[125I]-表螺环哌啶的结合减少> 36%（P < 0.05）。这些数据表明，暴露于MPTP而患帕金森病的猫整个纹状体中多巴胺再摄取位点数量显著减少，并且这些动物感觉运动功能的恢复与纹状体再摄取位点数量的增加无关。然而，行为恢复似乎与整个纹状体复合体中D1受体的普遍升高相关。目前的数据还表明，在大量多巴胺耗竭性损伤后多巴胺受体调节的变化与行为缺陷或从这些缺陷中恢复之间的直接关联很困难，并且多巴胺受体/转运体与行为之间的关系需要进一步研究。
