Immediate and long-term effects of neonatal MK-801 treatment on nonspatial learning

These experiments observed the immediate and long-term effects of neonatal treatment with MK-801 on patterned single alternation (PSA), a form of nonspatial, memory-based learning. Rat pups were injected daily on postnatal days (PND) 7–19, with MK-801 (MK(+)) or the less active isomer of MK-801 (MK(−)) (0.25 mg/kg), and trained at either PND 22 or 60. Rats treated with MK(+) or MK(−) and trained on PND 22 were significantly impaired in PSA when compared with the saline control. Beyond the learning impairment, MK(+) rats showed an overall decreased running speed during training. They also presented an array of abnormal behaviors and significant weight loss. These nonassociative variables were determined for several doses (0.025, 0.05, 0.1, 0.15, and 0.20 mg/kg) through PND days 22–25. Rats that received the threshold dose for secondary effects (0.025 mg/kg) also showed an overall decrease in running speed, but failed to show a significant nonspatial learning impairment on PSA. The PSA learning impairment was found to be not long lasting; rats trained at PND 60, after neonatally receiving the original high dose of MK-801, did not differ from controls.