Circadian variation in susceptibility to methamphetamine after repeated administration in mice

Since repeated administration of methamphetamine sometimes induces an augmentation in susceptibility, i.e., a reverse tolerance, to the stimulant drug effect in animals, the circadian variation in susceptibility to the ambulation-increasing effect of methamphetamine after repeated administration was investigated in mice. The ambulatory activity of each mouse was measured by a tilting-type round activity cage of 25 cm in diameter. Mice, which had been housed under a 12 hr light-dark schedule (light period; 6:00-18:00) for 5 weeks, were administered methamphetamine 1 or 2 mg/kg SC at one of 6 times of day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00) for 5 times at intervals of 7 days, and their ambulatory activities were measured for 3 hr after each administration. The repeated administration of methamphetamine induced a reverse tolerance to the ambulation-increasing effect of the drug, and the mean overall ambulatory activity counts on the 5th session were estimated to be 2-4 times as high as the corresponding activity counts on the 1st session. However, the circadian variation in susceptibility, which was at maximum during the late dark period (administration at 3:00) and at minimum during the late light period (administration at 15:00), was well maintained even after the repeated administration. When the time of day of the drug administration were changed by 12 hr on the 6th session, a marked increase in the activity counts was observed in the mice changed from 15:00 to 3:00, while a marked decrease was observed in the mice changed from 3:00 to 15:00.(ABSTRACT TRUNCATED AT 250 WORDS)