Development of tolerance to ambulation-increasing effect of scopolamine dependent on environmental factors in mice

Effects of repeated administration of scopolamine at 0.5, 2.0 and 8.0 mg/kg s.c. on ambulatory activity in mice were investigated. The drug was administered 5 times at intervals of daily, 3-4 days and weekly. The ambulation-increasing effect of scopolamine progressively decreased when the mice were put into a tilting-type round activity cage of 25 cm in diameter and 13 cm in height during the presence of the acute drug effect. The tolerance, once produced, was maintained even 1 month after the withdrawal. In contrast, development of tolerance to the ambulation-increasing effect of scopolamine could not be found when the mice were put into a glass jar with a 5.5 cm diameter, in which the ambulation was perfectly restricted, after each drug administration. The present results suggest that the tolerance to the ambulation-increasing effect of scopolamine induced by repeated administration may be elicited by an interaction between the experimental situation and the drug effect.