Budzynska Barbara, Boguszewska-Czubara Anna, Kruk-Slomka Marta, Kurzepa Jacek, Biala Grazyna
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4A Chodzki Street, 20-093, Lublin, Poland,
Neurochem Res. 2015 May;40(5):1083-93. doi: 10.1007/s11064-015-1566-5. Epub 2015 Apr 11.
The purpose of our experiment was to examine the influence of co-administration of nicotine and mephedrone on anxiety-like behaviors, cognitive processes and the nicotine-induced behavioral sensitization as well as processes connected with induction of oxidative stress in the brain of male Swiss mice. The results revealed that co-administration of subthreshold doses of mephedrone and nicotine (0.05 mg/kg each) exerted marked anxiogenic profile in the elevated plus maze and displayed pro-cognitive action in the passive avoidance paradigm (nicotine 0.05 mg/kg and mephedrone 2.5 mg/kg). Furthermore, one of the main findings of the present study was that mephedrone, administered alone at the dose not affecting locomotor activity of mice (1 mg/kg), enhanced the expression of nicotine-induced locomotor sensitization. Moreover, mephedrone administered with nicotine decreased general antioxidant status and catalase activity as well as antioxidant enzymes activity in the hippocampus and prefrontal cortex and increased concentration of malondialdehyde, an indicator of lipid peroxidation processes. Considering the likelihood that mephedrone is taken as a part of polydrug combination with nicotine, the effects of this combination on mammalian organisms have been confirmed in our study. Understanding the consequences of co-administration of psychoactive substances on the central nervous system and oxidative processes in the brain provide the important toxicological significance, and may be useful in polydrug intoxication treatment.
我们实验的目的是研究尼古丁与甲氧麻黄酮共同给药对雄性瑞士小鼠焦虑样行为、认知过程、尼古丁诱导的行为敏化以及与大脑氧化应激诱导相关过程的影响。结果显示,阈下剂量的甲氧麻黄酮与尼古丁(各0.05毫克/千克)共同给药在高架十字迷宫中呈现出明显的致焦虑特征,在被动回避范式中表现出促认知作用(尼古丁0.05毫克/千克,甲氧麻黄酮2.5毫克/千克)。此外,本研究的主要发现之一是,单独给予不影响小鼠运动活动剂量(1毫克/千克)的甲氧麻黄酮可增强尼古丁诱导的运动敏化表达。而且,甲氧麻黄酮与尼古丁共同给药会降低总体抗氧化状态、过氧化氢酶活性以及海马体和前额叶皮质中的抗氧化酶活性,并增加丙二醛浓度,丙二醛是脂质过氧化过程的指标。鉴于甲氧麻黄酮可能作为与尼古丁多药组合的一部分被使用,我们的研究证实了这种组合对哺乳动物机体的影响。了解精神活性物质共同给药对中枢神经系统和大脑氧化过程的后果具有重要的毒理学意义,可能有助于多药中毒的治疗。