Differential sensitization to ambulation-increasing effect of methamphetamine after repeated administration to mice...

We have demonstrated that repeated administration of methamphetamine (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 experiment, changes in the sensitization were investigated in mice after repeated pretreatments 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 received the same pretreatment repeatedly in the cages of 15, 20, 30 and 40 cm in diameter. The present results suggest that in accordance with the all-or-none law, development of the sensitization is affected by the size of the activity cage in which the animals have repeatedly experienced the acute drug effect.