Effects of neonatal MK-801 exposure on recognition memory and excitatory-inhibitory balance of hippocampus in adult female rats

Abstract

Objective To investigate the long-term effects of repeated neonatal administration of dizocipline maleate (MK-801), the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, on recognition memory and hippocampal excitatory-inhibitory balance at the synaptic level in adult female rats. Methods Neonatal female Sprague-Dawley (SD) rats were randomly divided into model group and control group. Rats were administrated subcutaneously with MK-801 or normal saline from postnatal day (PND) 5 to PND14 (0.25 mg/kg, twice daily). (1) Object-in-context recognition test was performed on PND73-75. (2) The expression levels of vesicular glutamate transporter 1(VGLUT1) and vesicular GABA transporter(VGAT) in hippocampus were detected by immunohistochemical staining. Results (1) The preference index of model group for new objects was significantly lower than that of the control group (t=-2.762, P=0.012). (2) There was no significant difference in the expression of VGLUT1 in hippocampus of MK-801 mode group(P>0.05). Compared with control group(48.19±2.10), the VGAT level of model group in CA1(39.60±2.19) was lower. Compared with control group(CA1: (0.99±0.05), CA3: (1.28±0.02), the ratio of VGLUT1/VGAT was significantly upregulated in CA1(1.16±0.05)and CA3(1.44±0.03)(P<0.05). Conclusion Early NMDA receptor inhibition produces long-term deleterious effects on associative recognition memory and excitatory-inhibitory balance of hippocampus in female rats. These biochemical abnormalities may contribute to cognitive impairments observed in this study. Key words: MK-801; N-methyl-D-aspartate receptor; Recognition memory; Excitatory-inhibitory imbalance; Rat