Kuribara H, Tadokoro S
Pharmacol Biochem Behav. 1982 Dec;17(6):1251-6. doi: 10.1016/0091-3057(82)90129-0.
The existence of circadian variation in methamphetamine- and apomorphine-induced change in ambulatory activity in mice was investigated. Adult male mice of dd strain, which had been housed on a 12 hr light-dark schedule (light period; 6:00-18:00) for 4 weeks, received injections of either methamphetamine HCl 1 or 2 mg/kg SC at one of six times of day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00), or apomorphine HCl 0.5 or 1 mg/kg SC at one of six times of day (3:30, 7:30, 11:30, 15:30, 19:30 and 23:30). The control animals were administered a physiological saline vehicle alone at the corresponding times of day. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 3 hr after methamphetamine, and for 1 hr after apomorphine. A circadian variation in the ambulatory activity was observed after the administration of the saline, methamphetamine and apomorphine. Here, the highest activity counts were found when the saline, methamphetamine and apomorphine were administered during the late dark period (3:00 or 3:30), while the lowest activity counts were found when the saline and apomorphine 1 mg/kg were administered during the mid light period (11:00 or 11:30), and methamphetamine 1 and 2 mg/kg and apomorphine 1 mg/kg were administered during the late light period (15:00 or 15:30). The circadian variation in methamphetamine-induced increase in the activity was abolished by a pretreatment with reserpine 2 mg/kg SC 4 hr before, but that of apomorphine was maintained even by the pretreatment with reserpine. The present results suggest that the methamphetamine- and apomorphine-induced increase in the ambulatory activity in mice is dependent on the time-of-day of the drug administration, and the occurrence is mainly due to a circadian variation in activity of the catecholaminergic systems in the brain.
研究了甲基苯丙胺和阿扑吗啡诱导的小鼠自主活动变化中的昼夜节律变化。将在12小时明暗周期（光照期：6:00 - 18:00）饲养4周的成年dd品系雄性小鼠，在一天中的六个时间点（3:00、7:00、11:00、15:00、19:00和23:00）之一皮下注射1或2mg/kg盐酸甲基苯丙胺，或在一天中的六个时间点（3:30、7:30、11:30、15:30、19:30和23:30）之一皮下注射0.5或1mg/kg盐酸阿扑吗啡。对照动物在相应的一天时间点仅给予生理盐水。在给予甲基苯丙胺后，用倾斜式活动笼测量每只小鼠3小时的自主活动，给予阿扑吗啡后测量1小时。在给予生理盐水、甲基苯丙胺和阿扑吗啡后观察到自主活动的昼夜节律变化。在此，当在黑暗后期（3:00或3:30）给予生理盐水、甲基苯丙胺和阿扑吗啡时，活动计数最高，而当在光照中期（11:00或11:30）给予生理盐水和1mg/kg阿扑吗啡，以及在光照后期（15:00或15:30）给予1和2mg/kg甲基苯丙胺和1mg/kg阿扑吗啡时，活动计数最低。在给药前4小时皮下注射2mg/kg利血平预处理可消除甲基苯丙胺诱导的活动增加的昼夜节律变化，但阿扑吗啡的昼夜节律变化即使经利血平预处理仍保持。目前的结果表明，甲基苯丙胺和阿扑吗啡诱导的小鼠自主活动增加取决于给药时间，其发生主要是由于大脑中儿茶酚胺能系统活动的昼夜节律变化。
