Enhancing effect of methamphetamine on ambulatory activity produced by repeated administration in mice

Effect of repeated administration of methamphetamine (MAM) on ambulatory activity was studied under various experimental conditions. Nine groups of mice received 10 doses of 1, 2 or 4 mg/kg MAM on a daily, 3-4 day or weekly schedule. Increases in activity were enhanced progressively in proportion to the number of MAM doses, but the extent varied with the dose and interval of repetition. One mg/kg caused slight enhancement under all conditions. In the case of 2 mg/kg, marked enhancement was observed until the 7th-8th administration in 3-7 day schedules, but poorer enhancement was elicited by daily administration. Four mg/kg of daily repetition caused no enhancement, because of marked stereotyped behavior which competed with ambulation. However, the enhancement was observed in the 3-7 day schedule when stereotyped behavior was not prominent. The enhancement was well maintained after a 2 months drug-free period. When a mouse was confined in a jar of small diameter to impede ambulation after MAM, the enhancement was blocked. These results suggest a possibility that learning of drug effect in association with environmental factors may play an important role in the enhancing effect.