Differential effects of N-methyl-D-aspartate receptor blockade during the second and third postnatal weeks on spatial working and reference memory in adult rats

The present study investigated the effects of chronic NMDA receptor blockade during different developmental age after birth on the performance of two kinds of spatial memory tasks. Rats were chronically treated with MK-801 only during the 2nd or 3rd postnatal week or both, and later they were trained in radial maze and Morris water maze tasks. In radial maze training, MK-801 treatment in the 2nd postnatal week significantly impaired learning as well as the treatment of both the 2nd and 3rd weeks did. On the other hand, in Morris water maze training, MK-801 treatment in the 2nd postnatal week resulted only in mild learning impairment, although the treatment of both the 2nd and 3rd weeks caused severe impairment. MK-801 treatment only during the 3rd postnatal week did not cause any detectable changes in performance of both radial maze and water maze learning. Results suggest the possibility that NMDA receptor blockade during the 2nd postnatal week has a major impact on the development of abilities including spatial working memory required for proper performance in radial maze task, and that NMDA receptor-dependent development of spatial reference memory that is primarily assessed in water maze task persists beyond the 2nd postnatal week.