Role of the central ascending neurotransmitter systems in the psychostimulant effects of caffeine.
Role of the central ascending neurotransmitter systems in the psychostimulant effects of caffeine.
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DOI：
10.3233/jad-2010-1400
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发表时间：
2010
影响因子：
4
通讯作者：
Ferre, Sergi
中科院分区：
文献类型：
--
作者：
Ferre, Sergi
关键词：
咖啡因是世界上消费最多的精神活性药物。它是一种非选择性腺苷受体拮抗剂，在大脑中主要针对腺苷A1和A2A受体。和经典的精神刺激剂一样，咖啡因也能产生运动激活、增强和唤醒的效果。这取决于咖啡因在中枢神经递质系统中抵消腺苷的多重影响的能力。运动和增强效应依赖于咖啡因释放腺苷对提升的多巴胺能系统施加的突触前和突触后刹车的能力。咖啡因通过靶向纹状体谷氨酸能终末的A1-A2A受体异构体和纹状体多巴胺能终末的A1受体(突触前制动)，诱导谷氨酸依赖和谷氨酸非依赖性的多巴胺释放。咖啡因的这些突触前效应因纹状体A2A-D2和A1-D1受体异构体的拮抗相互作用而释放突触后刹车而得到加强。咖啡因的唤醒作用依赖于腺苷作为一种内源性睡眠促进物质对多个相互关联的上行唤醒系统施加的多种抑制机制的阻断。这些机制包括A1受体直接介导的皮质顶叶基底前脑系统的调节，以及A2A受体间接介导的下丘脑组胺和食欲素能系统的调节。
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 systemand an indirect A2A-receptor mediated modulation of the hypothalamic histaminergic and orexinergic systems.