ABSTRACT-We have demonstrated that repeated administration of methampheta mine (MAP) 1 2 mg/kg, s. c. in a tilting-type round activity cage with a diameter of 20 cm (20 cm-cage) at 1 7 day intervals produces progressive enhancement of the ambulation-increasing effect (AIE), showing sensitization (reverse tolerance) in mice. However, almost no sensitization was observed when mice had been pretreated with the same doses of MAP but confined in a narrow environment repeatedly. In this ex periment, changes in the sensitization were investigated in mice after repeated pre treatments with MAP at 2 mg/kg at 3 4 day interval for 4 times in activity cages of 5 different sizes (5, 10, 15, 30 and 40 cm in diameter) in comparison with that of in the 20 cm-cage. AIE obtained after MAP in the 5 and 10-cm cages was not enhanced, whereas AIE was significantly enhanced in the cages of more than 15 cm in diameter. There was no significant difference in the enhanced AIE among the 4 groups that 're ceived the same pretreatment repeatedly in the cages of 15, 20, 30 and 40 cm in diam eter. The present results suggest that in accordance with the all-or-none law, develop ment of the sensitization is affected by the size of the activity cage in which the ani mals have repeatedly experienced the acute drug effect.
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