Sensitization to apomorphine-induced rotational behavior in 6-OHDA-lesioned rats: effects of NMDA antagonists on drug response.
Sensitization to apomorphine-induced rotational behavior in 6-OHDA-lesioned rats: effects of NMDA antagonists on drug response.
复制标题
6-OHDA 损伤大鼠对阿扑吗啡诱导的旋转行为的敏感性：NMDA 拮抗剂对药物反应的影响。
DOI：
10.1016/0006-8993(95)00322-h
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Mayer,A
中科院分区：
文献类型：
--
作者：
Gancher,S;Mayer,A
药物诱导的行为敏化的发展被认为是伴随帕金森病患者的长期左旋多巴治疗的许多运动并发症的基础。由于在动物模型中，某些多巴胺能行为的致敏性与NMDA神经传递的改变有关，我们试图确定NMDA拮抗剂是否可以阻断单侧黑质纹状体病变啮齿动物对多巴胺激动剂旋转效应的致敏性。单侧6-羟基多巴胺损伤的大鼠接受单次剂量或8次每日剂量的阿扑吗啡，每次剂量之前的NMDA拮抗剂MK-801或CPP。最后一次阿扑吗啡给药后3天，测量D1激动剂SKF 38393产生的盘旋行为。MK-801（0.1 mg/kg）单次给药可预防随后对SKF 38393的反应，但与对照组相比，在阿朴吗啡之前重复给予MK-801（0.1或0.3 mg/kg）或CPP（0.1 mg/kg）均未预防随后对SKF 38393的反应或减弱反应。尽管MK-801或CPP预处理，但每个慢性给药组均显示阿扑吗啡的旋转效应增加。这些数据表明，在单侧nigrostriatally损伤大鼠长期治疗阿朴吗啡的行为敏化不依赖于NMDA受体的刺激。
The development of drug-induced behavioral sensitization is thought to underlie many of the motor complications that accompany chronic L-DOPA treatment of patients with Parkinson's disease. As the development of sensitization to some dopaminergic behaviors has been linked to alterations in NMDA neurotransmission in animal models, we sought to determine whether or not NMDA antagonists can block the development of sensitization to rotational effects of dopamine agonists in rodents with unilateral nigrostriatal lesions. Rats with unilateral 6-hydroxydopamine lesions received either a single dose or eight daily doses of apomorphine, each dose preceded by the NMDA antagonists MK-801 or CPP. Three days after the last apomorphine dose, the circling behavior produced by the D1 agonist SKF 38393 was measured. A single dose of MK-801 (0.1 mg/kg) prevented the subsequent response to SKF 38393 but neither repeated treatment with MK-801 (0.1 or 0.3 mg/kg) nor CPP (0.1 mg/kg) preceding apomorphine prevented the subsequent response to SKF 38393 or attenuated the response in comparison to a control group. Each of the chronic treatment groups exhibited an increase in rotational effects of apomorphine despite MK-801 or CPP pretreatment. These data suggest behavioral sensitization in unilateral nigrostriatally lesioned rats chronically treated with apomorphine is not dependent upon stimulation of NMDA receptors.