Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Pharmacol Biochem Behav. 2010 Feb;94(4):561-9. doi: 10.1016/j.pbb.2009.11.011. Epub 2009 Dec 1.
Tremulous jaw movements in rats, which can be induced by dopamine (DA) antagonists, DA depletion, and cholinomimetics, have served as a useful model for studies of tremor. Although adenosine A(2A) antagonists can reduce the tremulous jaw movements induced by DA antagonists and DA depletion, there are conflicting reports about the interaction between adenosine antagonists and cholinomimetic drugs. The present studies investigated the ability of adenosine antagonists to reverse the tremorogenic effect of the muscarinic agonist pilocarpine. While the adenosine A(2A) antagonist MSX-3 was incapable of reversing the tremulous jaw movements induced by the 4.0mg/kg dose of pilocarpine, both MSX-3 and the adenosine A(2A) antagonist SCH58261 reversed the tremulous jaw movements elicited by 0.5mg/kg pilocarpine. Systemic administration of the adenosine A(1) antagonist DPCPX failed to reverse the tremulous jaw movements induced by either an acute 0.5mg/kg dose of the cholinomimetic pilocarpine or the DA D2 antagonist pimozide, indicating that the tremorolytic effects of adenosine antagonists may be receptor subtype specific. Behaviorally active doses of MSX-3 and SCH 58261 showed substantial in vivo occupancy of A(2A) receptors, but DPCPX did not. The results of these studies support the use of adenosine A(2A) antagonists for the treatment of tremor.
大鼠的下颌震颤运动可被多巴胺（DA）拮抗剂、DA 耗竭和拟胆碱药诱导，该模型已被广泛用于震颤研究。虽然腺苷 A(2A)拮抗剂可减少由 DA 拮抗剂和 DA 耗竭引起的下颌震颤运动，但关于腺苷拮抗剂与拟胆碱药之间的相互作用存在相互矛盾的报告。本研究探讨了腺苷拮抗剂逆转拟胆碱药毛果芸香碱引起震颤的能力。虽然腺苷 A(2A)拮抗剂 MSX-3 不能逆转 4.0mg/kg 毛果芸香碱剂量引起的下颌震颤运动，但 MSX-3 和腺苷 A(2A)拮抗剂 SCH58261 均能逆转 0.5mg/kg 毛果芸香碱引起的下颌震颤运动。腺苷 A(1)拮抗剂 DPCPX 全身给药不能逆转急性 0.5mg/kg 毛果芸香碱或 DA D2 拮抗剂匹莫齐特引起的下颌震颤运动，表明腺苷拮抗剂的震颤缓解作用可能具有受体亚型特异性。MSX-3 和 SCH 58261 的行为活性剂量对 A(2A)受体具有明显的体内占有率，但 DPCPX 则没有。这些研究的结果支持使用腺苷 A(2A)拮抗剂治疗震颤。
