Connole Laura, Harkin Andrew, Maginn Mark
Department of Safety Pharmacology, H. Lundbeck A/S, Valby, Copenhagen, Denmark.
Basic Clin Pharmacol Toxicol. 2004 Dec;95(6):299-304. doi: 10.1111/j.1742-7843.2004.pto950509.x.
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.
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。
