Cross interaction between methamphetamine and scopolamine by means of ambulatory activity in mice

Interaction between methamphetamine (MAP; 1 and 2 mg/kg, s.c.) and scopolamine (SCP; 0.5 and 2 mg/kg, s.c.) was investigated by means of ambulatory activity in mice of the dd strain. The single administration of MAP and SCP increased the ambulatory activity in a dose-dependent manner. The repeated administration of SCP, 5 times at intervals of 3-4 days, elicited a tolerance to its ambulation-increasing effect. The SCP-experienced mice showed no marked change in their sensitivity to the ambulation-increasing effect of MAP. However, when MAP was additionally administered, these mice showed a reverse tolerance to MAP. Such repeated administration of MAP was effective for attenuating the SCP-tolerance. On the other hand, the repeated MAP administration produced not only reverse tolerance to MAP itself but also cross reverse tolerance to SCP. However, as observed in the drug-naive mice, the MAP-experienced mice also exhibited tolerance to the additionally administered SCP. The repeated SCP administration scarcely modified the acquired MAP-reverse tolerance. The present results suggest that a cross reverse tolerance from MAP to SCP, but not from SCP to MAP, is developed in this mouse strain. It is also suggested that the reverse tolerance to MAP and tolerance to SCP appear regardless of the pretreatment of SCP and MAP, respectively, and that the reverse tolerance to MAP is well-maintained.