Locomotion elicited by MK801 in developing and adult rats: temporal, environmental, and gender effects

The effects of environmental novelty on locomotion elicited by an N-methyl-D-aspartate (NMDA) receptor antagonist, (+)MK-801 hydrogen maleate [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine], were investigated. Male and female rats aged 10, 20, 30 or 54-68 days were injected s.c. with MK801 and placed in activity monitors either immediately (no-delay) or after a 60 min delay (delay). In the no-delay condition, MK801 induced an inverse U-shaped dose-response effect on locomotion; peak activation occurred with 0.1 mg/kg and ataxia occurred with higher doses. The introduction of a novel environment 60 min after drug injection shifted the dose-effect function of MK801 to the left; i.e., in rats 20 days of age and older, the activity induced by 0.1 mg/kg MK801 was potentiated in the delay condition. For the 0.5 mg/kg dose, 20-day-olds showed activation in the no-delay condition but ataxia in the delay condition. This dose induced ataxia followed by activation in 30-day-olds and adult males or ataxia in adult females, regardless of delay condition. Age-, gender-, and novelty-dependent variations in MK801-induced locomotion may reflect differences in limbic-motor circuitry.