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纳洛酮可改善神经毒性甲基苯丙胺给药方案诱导的雄性大鼠空间记忆缺陷和体温过高。

Naloxone Ameliorates Spatial Memory Deficits and Hyperthermia Induced by a Neurotoxic Methamphetamine Regimen in Male Rats.

作者信息

Khalifeh Solmaz, Khodamoradi Mehdi, Hajali Vahid, Ghazvini Hamed, Eliasy Lelia, Kheradmand Afshin, Farnia Vahid, Akhtari Javad, Shahveisi Kaveh, Ghalehnoei Hossein

机构信息

Cognitive and Neuroscience Research Center (CNRC), Amiralmomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Substance Abuse Prevention Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Galen Med J. 2019 Apr 15;8:e1182. doi: 10.31661/gmj.v0i0.1182. eCollection 2019.

Abstract

BACKGROUND

Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats.

MATERIALS AND METHODS

The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/ kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task.

RESULTS

METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task.

CONCLUSION

The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory.

摘要

背景

甲基苯丙胺(METH)作为一种合成精神兴奋剂,正日益被视为一个全球性问题,它可能会导致记忆障碍。另一方面,众所周知,阿片类拮抗剂纳洛酮对学习和记忆有一些有益影响。本研究旨在评估纳洛酮对雄性大鼠因METH神经毒性方案引发的空间学习和记忆障碍的影响。

材料与方法

动物接受皮下(sc)注射METH方案(4×6mg/kg,间隔2小时)、腹腔内(ip)注射纳洛酮(4×1mg/kg,间隔2小时)或生理盐水,共进行四次注射。纳洛酮 - METH组大鼠在每次METH注射(6mg/kg,sc)前30分钟接受四次纳洛酮注射(1mg/kg,ip),间隔2小时。七天后,在莫里斯水迷宫(MWM)任务中评估它们的空间学习和记忆能力。

结果

METH方案在任务的获取和保持阶段引起体温过高以及表现不佳,表明与对照组相比存在空间学习和记忆障碍。每次METH注射前给予纳洛酮(1mg/kg,ip)可显著减轻体温过高以及METH对大鼠在MWM任务中表现的不利影响。

结论

结果表明,用阿片类拮抗剂纳洛酮预处理可预防METH对体温和记忆表现的不利影响。看来阿片肽系统和体温过高可能至少部分参与了METH对空间记忆的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f2e/8343598/f71bf48bc087/gmj-8-e1182-g001.jpg

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