Effect of NR2A specific antagonist NVP-AAM077 on spatial learning and memory in rats
- VernacularTitle:NR2A特异性拮抗剂NVP-AAM077对大鼠海马空间学习和记忆能力的影响
- Author:
Feng ZHENG
1
;
Zi-Han ZHANG
;
Jian-Zhou CHEN
;
Qing-Hua JIN
;
Bin XIAO
Author Information
- Keywords: NR2A; NVP-AAM077; hippocampus; dentate gyrus; spatial learning and memory; integrated stress response
- From: Chinese Pharmacological Bulletin 2024;40(8):1517-1522
- CountryChina
- Language:Chinese
- Abstract: Aim To observe the changes in hippocam-pal 2A subunit of N-methyl-D-aspartate receptor(NR2A)before and after the learning and memory training,and then investigate the neuropharmacological effects of NR2A by microinjection of NVP-AAM077(NR2A specific antagonist)into the hippocampal den-teta gyrus,based on the spatial learning and memory behavior paradigm induced by Mirror water maze train-ing.Methods Three-month old SD rats were random-ly divided into the training and non-training group,and the rats in the two groups were randomly divided into control group and NVP-AAM077 group(NVP).The expressions of NR2A,brain-derived neurotrophic factor(BDNF),transcriptional activator 4(ATF4)and eu-karyotic transcription initiation factor 2 α(eIF2α)phosphorylation levels in denteta gyrus were detected by Western blot.Then,integrated stress response in-hibitor ISRIB was microinjected into the dentate gyrus after the NVP,the expression of ATF4 and p-eIF2αlevels,and the spatial memory abilities were detected.Results Compared with non-training,behavioral training promoted the expression of NR2A and BDNF of rats in denteta gyrus,and this effect could be inhibi-ted by NVP,which significantly increased the expres-sion of p-eIF2α and ATF4.Injection of ISRIB into denteta gyrus significantly inhibited the expression of ATF4,and reversed the spatial memory impairment caused by NVP.Conclusion NVP-induced hipp-ocampal dentate gyrus NR2A-mediated spatial learning and memory impairment in rats may be related to hipp-ocampal integrated stress response.
