Effects of interdose interval on ambulatory sensitization to methamphetamine, cocaine and morphine in mice

Abstract

To determine the minimum interdose interval for induction of ambulatory sensitization to methamphetamine, cocaine and morphine, 3 sets of 5 groups of mice were treated with either methamphetamine (2 mg/kg s.c.), cocaine (10 mg/kg s.c.) or morphine (10 mg/kg s.c.) 3 times at intervals of 3, 6, 12, 24 or 48 h, and then 2 times at intervals of 3 days in all groups. During the first 3 administrations of both methamphetamine and cocaine, interdose intervals of 3-12 h did not produce a significant change in the ambulatory stimulation. However, 3 repeated administrations of morphine with interdose intervals of 3 and 6 h, but not 12 h, caused tolerance to the ambulatory stimulant effect. The administration of all drugs with interdose intervals of 24 and 48 h produced ambulatory sensitization. Furthermore, following the fourth and fifth administrations of each drug, all groups of mice demonstrated sensitization. These results indicate that an interdose interval of 24 h or longer is required for induction of ambulatory sensitization to methamphetamine, cocaine and morphine.