Effects of NMDA receptor blockers on cocaine-stimulated locomotor activity in mice

Effects of MK-801 and ketamine, N-methyl-D-aspartate (NMDA) receptor blockers, on cocaine-stimulated locomotor activity were investigated in male Swiss-Webster mice. MK-801 (0.25, 0.5, 1.0 and 2.5 mg/kg), ketamine (10, 25 and 50 mg/kg) or saline was injected 20 min before cocaine (5, 10 and 20 mg/kg i.p.). Locomotor activity was measured for 30 min immediately following cocaine treatment. All doses of the drugs were also tested for ability to depress or stimulate locomotor activity in the naive (no cocaine-treated) mice. Cocaine produced a dose-dependent increase in locomotor activity that was blocked dose-dependently by MK-801 or ketamine. The blockade by MK-801 was more prominent than by ketamine. Our results may suggest that cocaine-induced locomotor stimulation in mice is modulated via NMDA receptor mediated mechanisms.