THE CHARACTERISTICS OF REVERSE TOLERANCE TO THE AMBULATION-INCREASING EFFECT OF COCAINE AFTER REPEATED ADMINISTRATION IN MICE

Abstract

Effects of repeated subcutaneous administration of cocaine (COC) at doses of 10, 20 or 40 mg/kg at intervals of 1-7 days 5 times in mice placed individually into tilting activity cages of a sufficient size (20 cm in diameter and 15 cm height) were examined. A progressive enhancement of the ambulation-increasing effect was noted for 3-4 hrs after each administration, indicating that reverse tolerance had occurred. The doses of 10-20mg/kg and intervals of 3-7 days were optimal for producing clear reverse tolerance. The enhancement of the effect progressed rapidly and the maximal reverse tolerance was observed at the 3rd-4th administration and this enhancement lasted at least one month. However, higher doses of COC (40mg/kg) caused stereotypy concurrent with preconvulsive signs of short duration that were enhanced by serial administration. In contrast, pretreatments with the drug in a narrow environment (glass jar with a 5.5cm diameter and 15cm height) did not cause any enhancement. Cross-reverse tolerance occurred between COC and methamphetamine.