ABSTRACT
Objective To investigate the effects of repeated neonatal administration of dizocipline maleate (MK-801), the N-methyl-D-aspartate (NMDA) receptor antagonist, on the expression of NMDA receptor subunits NMDAR 1 (NR1), NMDAR2A (NR2A), NMDAR2B (NR2B) and the protein levels of nerve growth factor (NGF) in neonatal rats. Methods Neonatal Sprague-Dawley (SD) rats were randomly divided into research group and control group, with 15 ani-mals in each group. Rats were administrated subcutaneously with MK-801 or normal saline from postnatal day (PND) 5 to PND14 (0.25 mg/kg, twice a day). The expression levels of NR1, NR2A, NR2B and NGF were examined on PND15, PND42 and PND70 in the prefrontal cortex and hippocampus. Results At PND15 (neonatal period), there were no signifi-cant differences in the expression levels of NR1, NR2A, NR2B and NGF in the prefrontal cortex and hippocampus be- tween the two groups (P>0.05). At PND42 (adolescence), NGF protein levels in the prefrontal cortex was significantly low-er in research group than in control group [(56.19±37.87) vs. (152.54±53.92), P<0.01]. At PND70 (adulthood), the expres-sion of NR1, NR2A in the hippocampus was significantly higher in research group than in control group [NR1:(149.55%± 27.00%) vs. (100.00%±32.08%);NR2A:(171.54%±19.85%) vs. (100.00%±51.04%). P<0.05]. Conclusion Neonatal re-peated treatment of MK-801 increases the expression of NMDA receptor subunits NR1, NR2A in the hippocampus in adulthood while decreases the expression of NGF in the prefrontal cortex in adolescence, suggesting that neonatal block-ade of the NMDA receptor may influence the growth and development of the nervous system.