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腺苷A1受体阻断模拟咖啡因对乙醇诱导的运动不协调的减弱作用。

Adenosine A1 receptor blockade mimics caffeine's attenuation of ethanol-induced motor incoordination.

作者信息

Connole Laura, Harkin Andrew, Maginn Mark

机构信息

Department of Safety Pharmacology, H. Lundbeck A/S, Valby, Copenhagen, Denmark.

出版信息

Basic Clin Pharmacol Toxicol. 2004 Dec;95(6):299-304. doi: 10.1111/j.1742-7843.2004.pto950509.x.

Abstract

The effects of co-administration of caffeine and ethanol were assessed on the motor coordination of rats on the accelerating rotarod (accelerod). Ethanol (2.5 g/kg, orally) decreased motor performance on the accelerod. Co-administration of caffeine (5 and 20 mg/kg, orally) dose-dependently attenuated this ethanol-induced deficit. Caffeine (20 mg/kg, orally) alone did not affect motor performance in the test. As caffeine is a non-selective adenosine receptor antagonist the ability of adenosine A(1) and A(2A) receptor blockade to attenuate ethanol-induced motor incoordination was determined. Pre-treatment with the adenosine A(1) receptor antagonist DPCPX (5 mg/kg, intraperitoneally) attenuated ethanol (2.5 g/kg, orally)-induced motor incoordination. By contrast, prior administration of the adenosine A(2A) selective antagonist SCH 58261 (10 mg/kg intraperitoneally) had no effect on the ethanol-induced motor deficit. These data demonstrate that adenosine A(1) receptor blockade mimics the inhibitory action of caffeine on ethanol-induced motor incorordination, and may contribute to the ability of caffeine to offset the acute intoxicating actions of ethanol.

摘要

评估了咖啡因与乙醇联合给药对大鼠在加速转棒试验(加速旋转杆)中的运动协调性的影响。乙醇(2.5克/千克,口服)降低了大鼠在加速旋转杆上的运动表现。联合给予咖啡因(5毫克/千克和20毫克/千克,口服)剂量依赖性地减弱了这种乙醇诱导的缺陷。单独给予咖啡因(20毫克/千克,口服)对试验中的运动表现没有影响。由于咖啡因是一种非选择性腺苷受体拮抗剂,因此测定了腺苷A(1)和A(2A)受体阻断减弱乙醇诱导的运动不协调的能力。用腺苷A(1)受体拮抗剂DPCPX(5毫克/千克,腹腔注射)预处理减弱了乙醇(2.5克/千克,口服)诱导的运动不协调。相比之下,预先给予腺苷A(2A)选择性拮抗剂SCH 58261(10毫克/千克,腹腔注射)对乙醇诱导的运动缺陷没有影响。这些数据表明,腺苷A(1)受体阻断模拟了咖啡因对乙醇诱导的运动不协调的抑制作用,并且可能有助于咖啡因抵消乙醇急性中毒作用的能力。

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