Nikodijević O, Jacobson K A, Daly J W
Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Pharmacol Biochem Behav. 1993 Jan;44(1):199-216. doi: 10.1016/0091-3057(93)90299-9.
Chronic ingestion of caffeine by mice caused a marked reduction in locomotor exploratory activity. At least 4 days of withdrawal were required to restore activity to normal levels. Stimulatory effects of injected caffeine were lower in chronically treated mice and the biphasic dose-response (stimulatory followed by depressant) curve for injected caffeine was left shifted. Seven days of withdrawal were required before the dose-response curve to caffeine was identical to that of control mice. The depressant effects of a potent xanthine phosphodiesterase inhibitor, 1,3-dipropyl-7-methylxanthine, were blunted in caffeine-treated mice. The depressant effects of A1- and A2-selective adenosine analogs were enhanced after chronic caffeine. There was little or no effect of chronic caffeine on the stimulatory effects of dopaminergic agents (amphetamine, caffeine), while both depressant and stimulatory effects of cholinergic agents (nicotine, oxotremorine, scopolamine) were reduced. The results indicate that chronic caffeine affects functions of adenosine and cholinergic receptors related to regulation of locomotor exploratory activity.
小鼠长期摄入咖啡因会导致其自主探索活动显著减少。至少需要4天的戒断期才能使活动恢复到正常水平。在长期接受咖啡因处理的小鼠中，注射咖啡因的刺激作用较低，且注射咖啡因的双相剂量反应（先刺激后抑制）曲线向左移动。在咖啡因剂量反应曲线与对照小鼠相同之前，需要7天的戒断期。一种强效黄嘌呤磷酸二酯酶抑制剂1,3 - 二丙基 - 7 - 甲基黄嘌呤在咖啡因处理的小鼠中的抑制作用减弱。慢性咖啡因处理后，A1和A2选择性腺苷类似物的抑制作用增强。慢性咖啡因对多巴胺能药物（苯丙胺、咖啡因）的刺激作用几乎没有影响，而胆碱能药物（尼古丁、氧化震颤素、东莨菪碱）的抑制和刺激作用均降低。结果表明，慢性咖啡因会影响与自主探索活动调节相关的腺苷和胆碱能受体的功能。
