Naloxone reduces levodopa-induced dyskinesias and apomorphine-induced rotations in primate models of parkinsonism
Naloxone reduces levodopa-induced dyskinesias and apomorphine-induced rotations in primate models of parkinsonism
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DOI：
10.1007/s00702-002-0715-6
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发表时间：
2002-10-01
影响因子：
3.3
通讯作者：
Andrén, PE
中科院分区：
文献类型：
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作者：
Klintenberg, R;Svenningsson, P;Andrén, PE
通过原位杂交，发现左旋多巴/苄丝肼亚慢性治疗增加了多巴胺耗尽的纹状体中前脑啡肽原 A 和前脑啡肽原 B 的 mRNA。为了检查内源性阿片系统功能障碍是否可能是左旋多巴诱导的运动障碍发生的基础，在普通狨猴的两种帕金森病模型中研究了纳洛酮（一种阿片拮抗剂）对运动障碍的作用。 MPTP 治疗的猴子每日口服左旋多巴/苄丝肼，可缓解帕金森病症状，但会引起严重且可重复的运动障碍。在峰值剂量运动障碍期间皮下注射纳洛酮（0.1、0.2 或 0.5mg/kg），使用最高剂量可显着减轻运动障碍，使运动活动正常化，但不会改变抗帕金森效应。单侧 6-OHDA 损伤的狨猴接受皮下注射阿朴吗啡，这会导致对侧转向行为，通过同时给予纳洛酮，这种转向行为最多可减少 35%。综上所述，目前的结果表明内源性阿片系统在灵长类动物左旋多巴诱导的运动障碍的发病机制中可能发挥作用。
Using in situ hybridization, it was found that subchronic treatment with levodopa/benserazide increased preproenkephalin-A and preproenkephalin-B mRNAs in the dopamine-depleted striatum. In order to examine whether dysfunction of the endogenous opioid system may underlie the development of levodopa-induced dyskinesias, the effect of naloxone, an opioid antagonist, on dyskinesias was investigated in two models of parkinsonism in the common marmoset. MPTP-treated monkeys were administered a daily oral dose of levodopa/benserazide which relieved the parkinsonian symptoms but induced severe and reproducible dyskinetic movements. Naloxone (0.1, 0.2 or 0.5mg/kg) was given subcutaneously (s.c.) during peak-dose dyskinesia, which reduced the dyskinesias significantly using the highest dose, normalized the motor activity, but did not modify the antiparkinson effect. Unilaterally 6-OHDA-lesioned marmosets received apomorphine s.c., which caused a contralateral turning behavior that could be reduced up to 35 percent by concomitant administration of naloxone. Taken together the present results suggest a possible role for the endogenous opioid system in the pathogenesis of levodopa-induced dyskinesia in primates.