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孕期暴露于甲基苯丙胺会导致海马体中记忆和NMDA受体发育的长期改变。

Prenatal methamphetamine exposure induces long-lasting alterations in memory and development of NMDA receptors in the hippocampus.

作者信息

Šlamberová R, Vrajová M, Schutová B, Mertlová M, Macúchová E, Nohejlová K, Hrubá L, Puskarčíková J, Bubeníková-Valešová V, Yamamotová A

机构信息

Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Prague, Czech Republic.

出版信息

Physiol Res. 2014;63(Suppl 4):S547-58. doi: 10.33549/physiolres.932926.

DOI:10.33549/physiolres.932926
PMID:25669686
Abstract

Since close relationship was shown between drug addiction and memory formation, the aim of the present study was to investigate the effects of interaction between prenatal methamphetamine (MA) exposure and MA treatment in adulthood on spatial and non-spatial memory and on the structure of the N-methyl-D-aspartate (NMDA) receptors in the hippocampus. Adult male rats prenatally exposed to MA (5 mg/kg) or saline were tested in adulthood. Non-spatial memory was examined in the Object Recognition Test (ORT) and spatial memory in the Object Location Test (OLT) and in the Memory Retention Test (MRT) conducted in the Morris Water Maze (MWM), respectively. Based on the type of the memory test animals were injected either acutely (ORT, OLT) or long-term (MWM) with MA (1 mg/kg). After each testing, animals were sacrificed and brains were removed. The hippocampus was then examined in Western Blot analysis for occurrence of different NMDA receptors' subtypes. Our results demonstrated that prenatal MA exposure affects the development of the NMDA receptors in the hippocampus that might correspond with improvement of spatial memory tested in adulthood in the MWM. On the other hand, the effect of prenatal MA exposure on non-spatial memory examined in the ORT was the opposite. In addition, we showed that the effect of MA administration in adulthood on NMDA receptors is influenced by prenatal MA exposure, which seems to correlate with the spatial memory examined in the OLT.

摘要

由于药物成瘾与记忆形成之间存在密切关系,本研究旨在探讨产前暴露于甲基苯丙胺(MA)与成年期MA治疗之间的相互作用对空间和非空间记忆以及海马中N-甲基-D-天冬氨酸(NMDA)受体结构的影响。对成年雄性大鼠进行测试,这些大鼠在产前分别暴露于MA(5 mg/kg)或生理盐水。分别在物体识别测试(ORT)中检测非空间记忆,在物体位置测试(OLT)和莫里斯水迷宫(MWM)中进行的记忆保持测试(MRT)中检测空间记忆。根据记忆测试类型,动物急性(ORT、OLT)或长期(MWM)注射MA(1 mg/kg)。每次测试后,处死动物并取出大脑。然后在蛋白质印迹分析中检查海马中不同NMDA受体亚型的出现情况。我们的结果表明,产前暴露于MA会影响海马中NMDA受体的发育,这可能与成年期在MWM中测试的空间记忆改善相对应。另一方面,产前暴露于MA对ORT中检测的非空间记忆的影响则相反。此外,我们表明成年期给予MA对NMDA受体的影响受产前暴露于MA的影响,这似乎与OLT中检测的空间记忆相关。

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