Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands.
Food Chem Toxicol. 2021 Nov;157:112610. doi: 10.1016/j.fct.2021.112610. Epub 2021 Oct 12.
Methamphetamine (MA) is a psychostimulant and addictive substance. Long-term uses and toxic high doses of MA can induce neurotoxicity. The present study aimed to investigate the protective role of melatonin against MA toxicity-induced dysregulation of the neurotransmission related to cognitive function in rats. The adult male Sprague Dawley rats were intraperitoneally injected with 5 mg/kg MA for 7 consecutive days with or without subcutaneously injected with 10 mg/kg melatonin before MA injection. Some rats were injected with saline solution (control) or 10 mg/kg melatonin. MA administration induced reduction in total weight gain, neurotoxic features of stereotyped behaviors, deficits in cognitive flexibility, and significantly increased lipid peroxidation in the brain which diminished in melatonin pretreatment. The neurotoxic effect of MA on glutamate, dopamine and GABA transmitters was represented by the alteration of the GluR1, DARPP-32 and parvalbumin (PV) levels, respectively. A significant decrease in the GluR1 was observed in the prefrontal cortex of MA administration in rats. MA administration significantly increased the DARPP-32 but decreased PV in the striatum. Pretreatment of melatonin can abolish the neurotoxic effect of MA on neurotransmission dysregulation. These findings might reveal the antioxidative role of melatonin to restore neurotransmission dysregulation related to cognitive deficits in MA-induced neurotoxicity.
甲基苯丙胺（MA）是一种精神兴奋剂和成瘾物质。长期使用和高毒性剂量的 MA 会导致神经毒性。本研究旨在探讨褪黑素对 MA 毒性诱导的与认知功能相关的神经递质失调的保护作用。雄性成年 Sprague Dawley 大鼠连续 7 天腹腔注射 5mg/kg MA，或在 MA 注射前皮下注射 10mg/kg 褪黑素。一些大鼠注射生理盐水（对照）或 10mg/kg 褪黑素。MA 给药导致总体重增加减少、刻板行为的神经毒性特征、认知灵活性缺陷以及大脑脂质过氧化显著增加，而褪黑素预处理可减少这些变化。MA 对谷氨酸、多巴胺和 GABA 递质的神经毒性作用表现为 GluR1、DARPP-32 和 parvalbumin（PV）水平的改变。MA 给药可显著降低前额叶皮质中的 GluR1。MA 给药可显著增加纹状体中的 DARPP-32，但降低 PV。褪黑素预处理可消除 MA 对神经递质失调的神经毒性作用。这些发现可能揭示了褪黑素的抗氧化作用，以恢复 MA 诱导的神经毒性中与认知缺陷相关的神经递质失调。
