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美沙酮预处理对单日美沙酮毒性挑战的长期保护作用。

Long-term protective effects of methamphetamine preconditioning against single-day methamphetamine toxic challenges.

机构信息

Molecular Neuropsychiatry Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD 21224, USA.

出版信息

Curr Neuropharmacol. 2011 Mar;9(1):35-9. doi: 10.2174/157015911795017344.

DOI:10.2174/157015911795017344
PMID:21886558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3137197/
Abstract

Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH -induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems.

摘要

甲基苯丙胺（METH）的使用与神经毒性作用有关，包括大脑中多巴胺（DA）、5-羟色胺（5-HT）及其代谢物水平降低。我们已经表明，递增 METH 剂量可以在接受有毒 METH 挑战后 24 小时内牺牲的大鼠中对抗 METH 诱导的神经毒性。目前研究的目的是调查 METH 的保护作用是否能持续很长时间。我们还测试了第二次用有毒剂量 METH 进行的挑战是否会对单胺能末梢造成进一步的损害。在接受挑战后两周牺牲的大鼠中，盐水预处理的大鼠表现出明显的 METH 诱导的纹状体 DA 和 5-HT 水平降低。与单次 METH 挑战相比，接受两次 METH 挑战的大鼠纹状体 DA 或 5-HT 水平没有进一步降低。相比之下，METH 预处理大鼠对 METH 诱导的纹状体 DA 和 5-HT 耗竭表现出显著的保护作用。此外，METH 挑战会导致皮质 5-HT 水平大幅降低，而第二次药物挑战不会进一步增强这种降低。METH 预处理几乎完全防止了 METH 诱导的 5-HT 耗竭。这些结果与 METH 预处理使大脑对 METH 诱导的脑单胺能系统退化产生抗性的观点一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d49/3137197/4b359e07ea3c/CN-9-35_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d49/3137197/30598fdb96a1/CN-9-35_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d49/3137197/42ae6fc388bc/CN-9-35_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d49/3137197/4b359e07ea3c/CN-9-35_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d49/3137197/30598fdb96a1/CN-9-35_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d49/3137197/42ae6fc388bc/CN-9-35_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d49/3137197/4b359e07ea3c/CN-9-35_F3.jpg

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