Long-term effects of neonatal MK-801 treatment on spatial learning and cortical plasticity in adult rats

Rationale and objectives: The long-term effects of neonatal treatment with MK-801 on spatial learning and cortical plasticity were investigated in adult rats. Methods: Rat pups were injected twice daily with MK-801 (0.1 mg/kg) on postnatal days 7-19, participated in water maze testing between postnatal days 90 and 102, and were then studied electrophysiologically. Results: Treatment with MK-801 in such a low dose resulted in a very slight impairment of performance in the water maze task, but not in the visual cue response. Besides the slight learning impairment, the electrophysiological study revealed a reduction in the capacity for plasticity in the primary motor cortex of the treated animals, which was pronounced in the controls. Conclusion: The study demonstrates that even a slight impairment in learning and memory function may be accompanied by a cortical plasticity deficiency that is detectable electrophysiologically.