Effects of neonatal MK-801 exposure on recognition memory and excitatory-inhibitory balance of hippocampus in adult female rats
10.3760/cma.j.issn.1674-6554.2018.04.001
- VernacularTitle:新生期暴露MK-801对成年雌性大鼠再认记忆和海马兴奋-抑制平衡的影响
- Author:
Yue ZHANG
1
;
Yingying ZHAO
;
Jitao LI
;
Tianmei SI
;
Yunai SU
Author Information
1. 100191 北京,北京大学第六医院,北京大学精神卫生研究所,卫生部精神卫生学重点实验室(北京大学)
- Keywords:
MK-801;
N-methyl-D-aspartate receptor;
Recognition memory;
Excitatory-inhibitory imbalance;
Rat
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2018;27(4):289-293
- CountryChina
- Language:Chinese
-
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.