The repeated administration of ketamine induces an enhancement of its stimulant action in mice.

The modification of the stimulant and motor-incoordinate actions of ketamine induced by repeated administration was investigated by means of ambulatory activity and rota-rod performance in mice, respectively. Ketamine (12.5, 25 and 50 mg/kg, s.c.) increased the mouse's ambulation in a dose-dependent manner, and the repeated 5-times administration at 3- to 4-day intervals enhanced the increment effect. However, a disruption of the rota-rod performance by ketamine was not modified by the repeated treatment. These results suggest that a reverse tolerance to the stimulant action of ketamine is produced, and that a tolerance to its motor-incoordinate action may not cause the enhancement.