Comparison of dopamine receptor antagonists on hyperlocomotion induced by cocaine, amphetamine, MK-801 and the dopamine D1 agonist C-APB in mice
Comparison of dopamine receptor antagonists on hyperlocomotion induced by cocaine, amphetamine, MK-801 and the dopamine D1 agonist C-APB in mice
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DOI：
10.1007/s002130051055
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发表时间：
1999-08-01
影响因子：
3.4
通讯作者：
Shaw, G
中科院分区：
文献类型：
--
作者：
O'Neill, MF;Shaw, G
原理：直接或间接刺激多巴胺受体可增加小鼠的运动活动。确定D-1和D-2多巴胺受体在介导这种活性中所起的作用可能是困难的，因为用于研究这些现象的实验范式多种多样。目的：本研究旨在比较多巴胺D-1和D-2受体选择性拮抗剂对一系列兴奋剂诱导的多动症的作用。方法：使小鼠习惯于有机玻璃自发活动箱（30 × 30 × 30 cm），并通过光束中断测量活动。结果：氟哌啶醇和氯氮平均能减轻MK-801引起的多动性。氟哌啶醇仅在降低自发活动的剂量（0.1 mg/kg）下才有此作用，而氯氮平在对自发活动无影响的剂量（1.25 mg/kg）下可降低MK-801诱导的多动。D-1拮抗剂SCH 23390（0.01 mg/kg）减少苯丙胺诱导的过度运动（2.5毫克/千克），可卡因（10 mg/kg）和C-APB（1.0 mg/kg），剂量不一致地改变自发活动，而选择性D-2拮抗剂雷氯必利仅减弱苯丙胺诱导的过度运动，可卡因和C-APB的剂量超过显著减弱自发运动活动所需的最小剂量。MK-801（0.3 mg/kg）诱导的过度运动峰值潜伏期被SCH 23390（0.1 mg/kg）延迟，但活动峰值水平未降低。结论：本研究的结果表明，选择性阻断D-1受体抑制安非他明和可卡因诱导的小鼠多动症，但不MK-80诱导的自发活动。
Rationale: Direct or indirect stimulation of dopamine receptors increases locomotor activity in mice. Determining the role played by D-1 and D-2 dopamine receptors in the mediation of this activity can be difficult due to the wide variety of experimental paradigms used to investigate these phenomena. Objectives: This study set out to compare the role of selective antagonism of dopamine D-1 and D-2 receptors on the hyperactivity induced by a range of stimulants. Methods: Mice were habituated to perspex locomotor activity boxes (30x30x30 cm) and activity was measured via photobeam interrupts. Results: Haloperidol and clozapine both reduced the hyperactivity induced by MK-801. Haloperidol did so only at a dose that also decreased spontaneous activity (0.1 mg/kg), whereas clozapine reduced MK-801-induced hyperactivity at a dose that bad no effect on spontaneous activity (1.25 mg/kg). The D-1 antagonist SCH23390 (0.01 mg/kg) reduced hyperlocomotion induced by amphetamine (2.5 mg/kg), cocaine (10 mg/kg) and C-APB (1.0 mg/kg) at doses that did not consistently alter spontaneous activity, whereas the selective D-2 antagonist raclopride only attenuated the hyperlocomotion induced by amphetamine, cocaine and C-APB at doses in excess of the minimum dose required to attenuate spontaneous locomotor activity significantly. The latency to peak levels of hyperlocomotion induced by MK-801 (0.3 mg/kg) was delayed by SCH23390 (0.1 mg/kg) but peak levels of activity were not reduced. Conclusions: The results of the present study suggest that selective blockade of D-1 receptors suppresses amphetamine and cocaine-induced hyperactivity in mice but not MK-80-induced locomotor activity.