Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration
Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration
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DOI：
10.1038/sj.npp.1300167
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发表时间：
2003-07-01
影响因子：
7.6
通讯作者：
Ferré, S
中科院分区：
文献类型：
--
作者：
Karcz-Kubicha, M;Antoniou, K;Ferré, S
腺苷A（1）和A（2A）受体参与咖啡因的运动效应仍然是一个有争议的问题。本文比较了咖啡因、A_（1）受体拮抗剂CPT和A_（2A）受体拮抗剂MSX-3对选择性A_（1）受体激动剂CPA和A_（2A）受体激动剂CGS 21680的拮抗作用。CPT和MSX-3在相同剂量下产生运动激活，分别选择性地抵消CPA和CGS 2 1680诱导的运动抑制。咖啡因在产生运动激活的剂量下也抵消CPA和CGS 21680诱导的运动抑制，然而，咖啡因在抵消CPA方面不如CPT有效，在抵消CGS 21680方面甚至不如MSX-3有效。另一方面，当在习惯性动物中单独给药时，咖啡因比CPT或MSX-3产生更强的运动激活。当CPT和MSX-3共同给药时，获得了对运动激活的累加效应。总之，这些结果表明，急性给予咖啡因对大鼠的运动激活作用涉及A（1）和A（2A）受体的中枢阻滞。饮用水（1.0mg/ml）导致对咖啡因急性给药的运动效应的耐受性、对安非他明的耐受性缺乏、对MSX-3的明显耐受性（向其“钟形”剂量-反应曲线的左侧移动）和对CPT的真正交叉耐受性。本研究结果提示，对A（1）受体阻滞剂耐受性的形成可能是对咖啡因运动激活效应耐受性的主要原因，而耐受个体中咖啡因残留的运动激活效应可能主要是由于A（2A）受体阻滞剂所致。
The involvement of adenosine A(1) and A(2A) receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 2 1680 by caffeine, the selective A, receptor antagonist CPT, and the A(2A) receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 2 1680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation, However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 2 1680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motor activating effects of acutely administered caffeine in rats involve the central blockade of both A(1) and A(2A) receptors, Chronic exposure to caffeine in the. drinking water (1,0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT. The present results suggest that development of tolerance to the effects of A(1) receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A(2A) receptor blockade.