IMPORTANCE OF POST DRUG ENVIRONMENTAL-FACTORS FOR INDUCTION OF SENSITIZATION TO THE AMBULATION-INCREASING EFFECTS OF METHAMPHETAMINE AND COCAINE IN MICE

Mice given five repeated administrations of methamphetamine (MAP: 2 mg /kg SC) or cocaine (COC: 20 mg/kg SC) at 3-day intervals in a round ti lting-type activity cage (20 cm in diameter) showed sensitization to t he ambulation-increasing effect of each drug. The mean 3- or 2-h overa ll activity count at the fifth administration of MAP or COC, respectiv ely, was 2.3-2.5 times higher than that at the first administration. M ice given MAP or COC 4 times in round spaces (15-30 cm in diameter), w here the floor did not tilt, exhibited sensitization as strong as that demonstrated by mice given each drug in the activity cages, when the mice were given the fifth administration in the activity cages. In con trast, mice repeatedly given the drugs in spaces 4-9 cm in diameter ne ver, and those in space 12 cm in diameter only partially, exhibited se nsitization to MAP and COC. Furthermore, mice given MAP or COC 4 times in their home cages (25D x 20W x 15H cm, with ten mice in each cage) showed partial sensitization. Repeated administration of saline to mic e in activity cages, in the spaces 4-30 cm in diameter, or in the home cages did not cause significant change in the sensitivity to either M AP or COC. These results suggest that repeated experience of the stimu lant effect of drug and the resultant ambulation is required for induc tion of sensitization to MAP and COC in terms of ambulation in mice. I t is also suggested that spaces larger than 12 cm in diameter, which c orrespond to 2-2.5 times as long as the body length without tail, and no interference from other mice are required for induction of strong s ensitization to both MAP and COC.