Circadian variation in susceptibility to the ambulation-increasing effect of scopolamine in mice

Circadian variation in susceptibility to the ambulation-increasing effect of scopolamine in mice was investigated. The mice housed under a 12-hr light-dark situation (light period: 6:00-18:00 and dark period: 18:00-6:00) for 5 weeks were administered scopolamine HBr at 0.5 or 2 mg/kg s.c. at one of six times of the day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00), and the ambulatory activity was measured for 2 hr. Scopolamine induced a dose-dependent increase in the ambulatory activity. In addition, there was a clear circadian variation in the susceptibility to the ambulation-increasing effect of scopolamine. The highest and the lowest overall activity counts during the 2 hr observation period were found when the drug was administered at 3:00 and 15:00, respectively. The present results suggest that the susceptibility to scopolamine in mice is dependent on the time-of-day at which the drug is administered. The reasons which may induce this circadian variation in susceptibility to scopolamine are discussed.