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 tilting-type activity cage (20 cm in diameter) showed sensitization to the ambulation-increasing effect of each drug. The mean 3- or 2-h overall activity count at the fifth administration of MAP or COC, respectively, was 2.3-2.5 times higher than that at the first administration. Mice given MAP or COC 4 times in round spaces (15-30 cm in diameter), where 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 contrast, mice repeatedly given the drugs in spaces 4-9 cm in diameter never, and those in space 12 cm in diameter only partially, exhibited sensitization 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 mice 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 MAP or COC. These results suggest that repeated experience of the stimulant effect of drug and the resultant ambulation is required for induction of sensitization to MAP and COC in terms of ambulation in mice. It is also suggested that spaces larger than 12 cm in diameter, which correspond 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 sensitization to both MAP and COC.