Abstract

Methamphetamine (METH) is a potent psychostimulant drug with an increasing rate of abuse over recent years. Depressive-like behaviors are one of the major symptoms patients in the METH withdrawal period experience. There is limited evidence regarding the METH withdrawal treatment, and conventional managements are not completely effective. Furthermore, extensive promising literature supports minocycline, a well-known antibiotic with anti-oxidant, anti-inflammatory properties, to treat depressive-like behaviors. Therefore, we hypothesized that administration of minocycline might mitigate the methamphetamine (METH) induced depression in male mice. Administration of METH (2 mg/kg) to mice two times a day for 14 constitutive days was done to induce the METH-induced withdrawal syndrome model. Animals were divided into 10 groups (n = 10 in each group), and three doses of minocycline (2.5, 5 and 10 mg/kg) were daily administered to male albino mice for 10 days. Following the behavioral test, the animals were scarified, their hippocampus were dissected to measure oxidative stress parameters. Our data revealed that chronic administration of minocycline provoked antidepressant effects in behavioral tests, such as forced swim test (FST), tail suspension test (TST) and splash test. Additionally, minocycline was able to improve oxidative stresses and neuronal damage in the hippocampus and restore the body’s antioxidant system by increasing glutathione (GSH) and the cellular energy (ATP) and reducing the malondialdehyde (MDA) level. According to our promising results of minocycline on targeting mitochondria and its performance, we suggest minocycline as a new therapeutic option in clinical trials of depression treatment.

摘要

甲基苯丙胺 (METH) 是一种强效精神兴奋药物，近年来滥用率不断上升。抑郁样行为是患者在 METH 戒断期间经历的主要症状之一。关于 METH 戒断治疗的证据有限，常规管理并不完全有效。此外，大量有前途的文献支持米诺环素（一种众所周知的具有抗氧化、抗炎特性的抗生素）来治疗抑郁样行为。因此，我们假设服用米诺环素可能会减轻甲基苯丙胺 (METH) 诱导的雄性小鼠抑郁症。每天两次向小鼠施用 METH (2 mg/kg)，持续 14 天，以诱导 METH 诱导的戒断综合征模型。将动物分为10组（n = 每组 10 只），每天向雄性白化病小鼠施用三剂米诺环素（2.5、5 和 10 mg/kg），持续 10 天。在行为测试之后，将动物划伤，解剖它们的海马体以测量氧化应激参数。我们的数据显示，长期服用米诺环素会在行为测试中引发抗抑郁作用，例如强迫游泳测试 (FST)、悬尾测试 (TST) 和飞溅测试。此外，米诺环素能够通过增加谷胱甘肽 (GSH) 和细胞能量 (ATP) 以及降低丙二醛 (MDA) 水平来改善海马中的氧化应激和神经元损伤，并恢复身体的抗氧化系统。根据我们对米诺环素靶向线粒体及其性能的有希望的结果，