National Institute on Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224, USA.
J Alzheimers Dis. 2010;20 Suppl 1(Suppl 1):S35-49. doi: 10.3233/JAD-2010-1400.
Caffeine is the most consumed psychoactive drug in the world. It is a non-selective adenosine receptor antagonist that in the brain targets mainly adenosine A1 and A2A receptors. The same as classical psychostimulants, caffeine produces motor-activating, reinforcing and arousing effects. This depends on the ability of caffeine to counteract multiple effects of adenosine in the central ascending neurotransmitter systems. Motor and reinforcing effects depend on the ability of caffeine to release pre- and postsynaptic brakes that adenosine imposes on the ascending dopaminergic system. By targeting A1-A2A receptor heteromers in striatal glutamatergic terminals and A1 receptors in striatal dopaminergic terminals (presynaptic brake), caffeine induces glutamate-dependent and glutamate-independent release of dopamine. These presynaptic effects of caffeine are potentiated by the release of the postsynaptic brake imposed by antagonistic interactions in the striatal A2A-D2 and A1-D1 receptor heteromers. Arousing effects of caffeine depend on the blockade of multiple inhibitory mechanisms that adenosine, as an endogenous sleep-promoting substance, exerts on the multiply interconnected ascending arousal systems. Those mechanisms include a direct A1-receptor mediated modulation of the corticopetal basal forebrain system and an indirect A2A-receptor mediated modulation of the hypothalamic histaminergic and orexinergic systems.
咖啡因是世界上使用最广泛的精神活性药物。它是非选择性的腺苷受体拮抗剂，在大脑中主要靶向腺苷 A1 和 A2A 受体。与经典的精神兴奋剂一样，咖啡因具有运动激活、强化和兴奋作用。这取决于咖啡因对抗中枢上行神经递质系统中多种腺苷作用的能力。运动和强化作用取决于咖啡因抵消腺苷对上行多巴胺能系统施加的突触前和突触后制动的能力。通过靶向纹状体内谷氨酸能末梢的 A1-A2A 受体异源二聚体和纹状体内多巴胺能末梢的 A1 受体（突触前制动），咖啡因诱导依赖于谷氨酸和非依赖于谷氨酸的多巴胺释放。咖啡因的这些突触前作用通过拮抗作用在纹状体 A2A-D2 和 A1-D1 受体异源二聚体中释放的突触后制动而增强。咖啡因的兴奋作用取决于对多种抑制机制的阻断，这些机制包括作为内源性促睡眠物质的腺苷对多重相互连接的上行唤醒系统的直接 A1 受体介导的调制和间接 A2A 受体介导的对下丘脑组胺能和食欲素能系统的调制。
