Acquas Elio, Tanda Gianluigi, Di Chiara Gaetano
Department of Toxicology, University of Cagliari, and Centre for Neuropharmacology - CNR, Via Ospedale72, I-09124, Cagliari, Italy.
Neuropsychopharmacology. 2002 Aug;27(2):182-93. doi: 10.1016/S0893-133X(02)00290-7.
The effects of caffeine on extracellular dopamine and acetylcholine have been studied in freely moving rats implanted with concentric microdialysis probes in the nucleus accumbens shell and core and in the medial prefrontal cortex. Intravenous administration of caffeine (0.25, 0.5, 1.0, 2.5 and 5.0 mg/kg) dose-dependently increased dopamine and acetylcholine dialysate concentrations in the medial prefrontal cortex, while it did not affect dialysate dopamine in the shell and core of the nucleus accumbens. Intraperitoneal administration of caffeine (1.5, 3, 10, 30 mg/kg) also failed to affect DA in the shell and core of the nucleus accumbens. Such effects were duplicated by intravenous administration of DPCPX, a selective antagonist of adenosine A1 receptors, and of SCH 58261, an antagonist of A2a receptors. The effect of caffeine on prefrontal dopamine and acetylcholine transmission was also studied in rats chronically administered with caffeine (25 mg/kg, twice a day for seven days). At the end of this treatment rats became tolerant to the locomotor stimulating effects of a dose of 1 and 2.5 mg/kg i.v. of caffeine; these doses, however, still increased dialysate acetylcholine but did not affect dopamine in the prefrontal cortex. Therefore, in rats made tolerant to the locomotor stimulant effects of caffeine, tolerance developed to the dopamine stimulant but not to the acetylcholine stimulant effect of caffeine in the prefrontal cortex. The lack of acute stimulation of dopamine release in the nucleus accumbens shell by caffeine is relevant to the issue of its addictive properties and of the role of DA in drug- and substance-addiction. On the other hand, the dissociation between tolerance to the locomotor effects of caffeine and stimulation of acetylcholine release in the prefrontal cortex suggests that this effect might be correlated to the arousing effects of caffeine as distinct from its locomotor stimulant properties.
咖啡因对细胞外多巴胺和乙酰胆碱的影响已在自由活动的大鼠中进行了研究，这些大鼠在伏隔核壳部、核心以及内侧前额叶皮质植入了同心微透析探针。静脉注射咖啡因（0.25、0.5、1.0、2.5和5.0毫克/千克）剂量依赖性地增加了内侧前额叶皮质中多巴胺和乙酰胆碱的透析液浓度，而对伏隔核壳部和核心的透析液多巴胺没有影响。腹腔注射咖啡因（1.5、3、10、30毫克/千克）也未能影响伏隔核壳部和核心的多巴胺。静脉注射腺苷A1受体选择性拮抗剂DPCPX和A2a受体拮抗剂SCH 58261也出现了类似效果。还对长期给予咖啡因（25毫克/千克，每天两次，共七天）的大鼠进行了咖啡因对前额叶多巴胺和乙酰胆碱传递影响的研究。在这种处理结束时，大鼠对静脉注射1和2.5毫克/千克咖啡因的运动刺激作用产生了耐受性；然而，这些剂量仍然增加了透析液中的乙酰胆碱，但不影响前额叶皮质中的多巴胺。因此，在对咖啡因的运动刺激作用产生耐受性的大鼠中，对咖啡因在前额叶皮质中的多巴胺刺激作用产生了耐受性，但对乙酰胆碱刺激作用未产生耐受性。咖啡因对伏隔核壳部多巴胺释放缺乏急性刺激作用与其成瘾特性以及多巴胺在药物和物质成瘾中的作用问题相关。另一方面，对咖啡因运动作用的耐受性与前额叶皮质中乙酰胆碱释放刺激之间的分离表明，这种作用可能与其不同于运动刺激特性的唤醒作用相关。
