AGE-DEPENDENT INDUCTION AND MAINTENANCE OF SENSITIZATION TO METHAMPHETAMINE-INDUCED HYPERACTIVITY IN MICE

Repeated administrations of methamphetamine (2 mg/kg, s.c.), 10 times at 3-day intervals, induced ambulatory sensitization in all groups of mice that were 13-, 15-, 19-, 23- and 36-weeks-old at the start of met hamphetamine administration. The most prominent sensitization was obse rved in the 19-week-old mice. Among five groups of mice, even though t he mice of 36 weeks old showed the highest sensitivity to methamphetam ine at the first administration, they exhibited the lowest sensitizati on during the latter stage of repeated methamphetamine administration. Methamphetamine sensitization once established was well reproduced by the post-sensitization period of 8 weeks. Furthermore, the group of m ice given methamphetamine with post-sensitization interval of 8 weeks (19-week-old mice) exhibited further enhancement of the sensitization. In contrast, the groups of mice given methamphetamine with post-sensi tization intervals of 12 and 25 weeks (the 23- and 36-week-old, respec tively) showed a significant reduced sensitization, and the latter gro up failed to reach the level of sensitization previously established. These results suggest that the induction of and maintenance of methamp hetamine sensitization are dependent on the age of the mice, and that methamphetamine sensitization once established completely persists for up to 8 weeks.