Klongpanichapak Sirirat, Govitrapong Piyarat, Sharma Sushil K, Ebadi Manuchair
Department of Pharmacology, Physiology and Therapeutics, School of Medicine & Health Sciences, University of North Dakota, 501 North Columbia Road, Grand Forks, ND, 58203, USA.
Neurochem Res. 2006 Mar;31(3):303-11. doi: 10.1007/s11064-005-9025-3.
The neurotoxic effects of cocaine and methamphetamine (METH) were studied in mice brain with a primary objective to determine the neuroprotective potential of coenzyme Q10 (CoQ10) in drug addiction. Repeated treatment of cocaine or METH induced significant reduction in the striatal dopamine and CoQ10 in mice. Cocaine or METH-treated mice exhibited increased thiobarbituric acid reactive substances (TBARs) in the striatum and cerebral cortex without any significant change in the cerebellum. Complex I immunoreactivity was inhibited in both cocaine and METH-treated mice, whereas tyrosine hydroxylase (TH) immunoreactivity was decreased in METH-treated mice and increased in cocaine-treated mice. Neither cocaine nor METH could induce significant change in alpha-synuclein expression at the doses and duration we have used in the present study. CoQ10 treatment attenuated cocaine and METH-induced inhibition in the striatal 18F-DOPA uptake as determined by high-resolution microPET neuroimaging. Hence exogenous administration of CoQ10 may provide neuroprotection in drug addiction.
研究了可卡因和甲基苯丙胺（冰毒）对小鼠大脑的神经毒性作用，主要目的是确定辅酶Q10（CoQ10）在药物成瘾方面的神经保护潜力。对小鼠重复给予可卡因或冰毒会导致纹状体多巴胺和CoQ10显著减少。经可卡因或冰毒处理的小鼠纹状体和大脑皮质中的硫代巴比妥酸反应性物质（TBARs）增加，而小脑无明显变化。在经可卡因和冰毒处理的小鼠中，复合体I免疫反应性均受到抑制，而经冰毒处理的小鼠酪氨酸羟化酶（TH）免疫反应性降低，经可卡因处理的小鼠则升高。在本研究中所使用的剂量和持续时间下，可卡因和冰毒均未诱导α-突触核蛋白表达发生显著变化。通过高分辨率微型PET神经成像测定，CoQ10治疗减轻了可卡因和冰毒诱导的纹状体18F-DOPA摄取抑制。因此，外源性给予CoQ10可能为药物成瘾提供神经保护作用。
