Zanjan Applied Pharmacology Research Center, Zanjan University of Medical sciences, Zanjan, Iran.
Departments of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Drug Chem Toxicol. 2022 Sep;45(5):2319-2327. doi: 10.1080/01480545.2021.1942484. Epub 2021 Jun 28.
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 ( = 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.
甲基苯丙胺（METH）是一种强效的精神兴奋剂药物，近年来滥用率不断上升。抑郁样行为是 METH 戒断期患者主要经历的症状之一。关于 METH 戒断治疗的证据有限，传统的治疗方法并不完全有效。此外，大量有前景的文献支持米诺环素，一种具有抗氧化、抗炎特性的知名抗生素，用于治疗抑郁样行为。因此，我们假设米诺环素的给药可能会减轻雄性小鼠中 METH 引起的抑郁。每天两次给小鼠注射 METH（2mg/kg）共 14 天，以诱导 METH 戒断综合征模型。动物分为 10 组（每组 10 只），每日给雄性白化小鼠给予三种剂量的米诺环素（2.5、5 和 10mg/kg），共 10 天。在行为测试后，处死动物，取出其海马体以测量氧化应激参数。我们的数据显示，慢性给予米诺环素在行为测试中表现出抗抑郁作用，如强迫游泳测试（FST）、悬尾测试（TST）和溅水测试。此外，米诺环素能够通过增加谷胱甘肽（GSH）和细胞能量（ATP）以及减少丙二醛（MDA）水平来改善海马体的氧化应激和神经元损伤，并恢复机体的抗氧化系统。根据我们在米诺环素针对线粒体及其性能方面的有希望的结果，我们建议将米诺环素作为治疗抑郁症临床试验中的一种新的治疗选择。
