Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease
Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease
复制标题
DOI：
10.1002/mds.10289
复制
发表时间：
2002-11-01
影响因子：
8.6
通讯作者：
Brotchie, J
中科院分区：
文献类型：
--
作者：
Fox, SH;Henry, B;Brotchie, J
长期用左旋多巴治疗帕金森病导致运动波动的发展，包括抗帕金森病作用和不自主运动的持续时间减少，即，左旋多巴诱发的运动障碍大麻素受体集中在基底神经节中，并且大麻素受体的刺激可以增加苍白球外侧段中的γ-氨基-丁酸传递并减少纹状体中的谷氨酸释放。因此，我们测试的假设，大麻素受体激动剂nabilone（0.01，0.03，和0.10毫克/公斤）将减轻左旋多巴诱导的运动障碍，在1-甲基-4-苯基-1，2，3，6-四氢吡啶盐酸盐（MPTP）-帕金森病的损伤绒猴模型。与左旋多巴单独给药相比，那比隆（0.1 mg/kg）与左旋多巴联合给药与显著较少的总运动障碍（运动障碍评分，12;范围，6-17;灵长类动物运动障碍评定量表）相关（22;范围，14-23; P < 0.05）。这种作用在发作期间（左旋多巴后0-20分钟）更显著。左旋多巴的抗帕金森病作用没有减弱。此外，中等剂量的那比隆（0.03 mg/kg）使左旋多巴抗帕金森病作用的持续时间增加了76%。因此，大麻素受体激动剂可用于治疗帕金森病的运动并发症。(C)2002年运动障碍协会。
Long-term treatment with levodopa in Parkinson's disease results in the development of motor fluctuations, including reduced duration of antiparkinsonian action and involuntary movements, i.e., levodopa-induced dyskinesia. Cannabinoid receptors are concentrated in the basal ganglia, and stimulation of cannabinoid receptors can increase gamma-amino-butyric acid transmission in the lateral segment of globus pallidus and reduce glutamate release in the striaturn. We thus tested the hypothesis that the cannabinoid receptor agonist nabilone (0.01, 0.03, and 0.10 mg/kg) would alleviate levodopa-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-lesioned marmoset model of Parkinson's disease. Coadministration of nabilone (0.1 mg/kg) with levodopa was associated with significantly less total dyskinesia (dyskinesia score, 12; range, 6-17; primate dyskinesia rating scale) than levodopa alone (22; range, 14-23; P < 0.05). This effect was more marked during the onset period (0-20 minutes post levodopa). There was no reduction in the antiparkinsonian action of levodopa. Furthermore, the intermediate dose of nabilone used (0.03 mg/kg) increased the duration of antiparkinsonian action of levodopa by 76%. Thus, cannabinoid receptor agonists may be useful in the treatment of motor complications in Parkinson's disease. (C) 2002 Movement Disorder Society.