Sinton C M, Petitjean F
Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, NJ 07901.
Pharmacol Biochem Behav. 1989 Feb;32(2):459-62. doi: 10.1016/0091-3057(89)90179-2.
Caffeine (20 mg/kg/day) was administered per os to 5 cats for 21 days and sleep parameters were measured both during drug administration and over the withdrawal phase. The initial effect of caffeine was a marked increase in waking. As the animal habituated to the stimulant action of the methylxanthine, however, total sleep time normalized, although time spent in Stage II slow wave sleep (S2) remained below, and Stage I slow wave sleep (S1) above, control levels throughout the period of drug administration. In contrast, a significant increase in the S2/S1 ratio was recorded as soon as caffeine treatment ended, and this parameter remained elevated for about 30 days. Chronic caffeine administration has been previously shown to increase the number of central adenosine receptors, and it has also been reported that adenosine agonists increase S2 at the expense of S1. The present data were thus interpreted as indicating that the action of caffeine on sleep may be mediated at a central adenosine receptor site. Results also imply that changes induced in this receptor population by chronic caffeine administration last for at least 30 days after the drug is withdrawn.
对5只猫经口给予咖啡因（20毫克/千克/天），持续21天，并在给药期间和撤药阶段测量睡眠参数。咖啡因的初始作用是显著增加觉醒。然而，随着动物对甲基黄嘌呤的刺激作用产生习惯，总睡眠时间恢复正常，尽管在整个给药期间，II期慢波睡眠（S2）的时间仍低于对照水平，而I期慢波睡眠（S1）的时间高于对照水平。相反，一旦咖啡因治疗结束，S2/S1比值就显著增加，并且该参数在约30天内一直保持升高。先前已表明，长期给予咖啡因会增加中枢腺苷受体的数量，并且也有报道称腺苷激动剂会以牺牲S1为代价增加S2。因此，目前的数据被解释为表明咖啡因对睡眠的作用可能是通过中枢腺苷受体部位介导的。结果还表明，长期给予咖啡因引起的该受体群体的变化在撤药后至少持续30天。
