Animal studies have consistently observed neuronal death following methamphetamine (MA) administration, however, these have not been systematically reviewed. This systematic review aims to present the evidence for MA-induced neuronal death in animals (rodents) and identify the regions affected. Locating the brain regions in which neuronal death occurs in animal studies will provide valuable insight into the linkage between MA consumption and the structural alterations observed in the human brain. The data were collected from three databases: Scopus, Ovid, and the Web of Science. Thirty-seven studies met the inclusion criteria and were divided into two sub-groups, i.e. acute and repeated administration. Twenty-six (of 27) acute and ten (of 11) repeated administration studies observed neuronal death. A meta-analysis was not possible due to different variables between studies, i.e. species, treatment regimens, withdrawal periods, methods of quantification, and regions studied. Acute MA treatment induced neuronal death in the frontal cortex, striatum, and substantia nigra, but not in the hippocampus, whereas repeated MA administration led to neuronal loss in the hippocampus, frontal cortex, and striatum. In addition, when animals self-administered the drug, neuronal death was observed at much lower doses than the doses administered by experimenters. There is some overlap in the regions where neuronal death occurred in animals and the identified regions from human studies. For instance, gray matter deficits have been observed in the prefrontal cortex and hippocampus of MA users. The findings presented in this review implicate that not only does MA induce neuronal death in animals, but it also damages the same regions affected in human users. Despite the inter-species differences, animal studies have contributed significantly to addiction research, and are still of great assistance for future research with a more relevant model of compulsive drug use in humans.

中文翻译：

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甲基苯丙胺诱导神经元死亡：来自啮齿动物研究的证据。

动物研究一直观察到甲基苯丙胺（MA）给药后神经元死亡，但是，尚未对它们进行系统地审查。这项系统的综述旨在为动物（啮齿动物）中MA引起的神经元死亡提供证据，并确定受影响的区域。在动物研究中确定发生神经元死亡的大脑区域，将为了解MA摄入与人脑中观察到的结构改变之间的联系提供有价值的见解。数据是从三个数据库收集的：Scopus，Ovid和Web of Science。三十七项研究符合纳入标准，分为急性和重复给药两个亚组。二十六个（共27个）急性和十个（共11个）重复给药研究观察到神经元死亡。由于研究之间存在不同的变量，因此无法进行荟萃分析，即物种，治疗方案，停药期，定量方法和研究区域。急性MA治疗可引起额叶皮质，纹状体和黑质神经元死亡，但不会引起海马体神经元死亡，而反复MA给药可导致海马，额叶皮质和纹状体神经元丧失。另外，当动物自我给药时，观察到神经元死亡的剂量远低于实验者给药的剂量。在动物发生神经元死亡的区域和根据人体研究确定的区域中存在一些重叠。例如，已经在MA使用者的前额叶皮层和海马体中观察到灰质缺乏。这篇综述中的发现暗示，MA不仅会诱导动物神经元死亡，而且还会损害人类使用者受到影响的相同区域。尽管物种间存在差异，但动物研究对成瘾性研究做出了重大贡献，并且仍以更相关的人类强迫性药物使用模型为以后的研究提供了巨大帮助。