Circadian variation in methamphetamine- and apomorphine-induced increase in ambulatory activity in mice.

Abstract

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.