Biala G, Pekala K, Boguszewska-Czubara A, Michalak A, Kruk-Slomka M, Budzynska B
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A Street, 20-093, Lublin, Poland.
Department of Medical Chemistry, Medical University of Lublin, Chodzki 4A Street, 20-093, Lublin, Poland.
Mol Neurobiol. 2017 Mar;54(2):904-921. doi: 10.1007/s12035-016-9701-0. Epub 2016 Jan 18.
Nicotine, the main component of tobacco smoke, exerts influence on mood, and contributes to physical and psychological dependence. Taking into account frequent concomitance of nicotine abuse and stress, we aimed to research behavioral and biochemical effects associated with nicotine administration in combination with chronic unpredictable mild stress (CUMS). Mice were submitted to the procedure of CUMS for 4 weeks, 2 h per day. Our results revealed that CUMS-exposed animals exhibited behavioral alteration like anxiety disorders in the elevated plus maze (EPM) test, the disturbances in memory in the passive avoidance (PA) test and depressive effects in the forced swim test (FST). Moreover, nicotine (0.05-0.5 mg/kg), after an acute or subchronic administration decreased stress-induced depression- and anxiety-like effect as well as memory deficit. Administration of metyrapone (50 mg/kg), a glucocorticosteroid antagonist, alleviated the depressive effect induced by the CUMS. The biochemical experiments showed decreased values of the total antioxidant status (TAS), activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) with simultaneously increased in malondialdehyde (MDA) concentration in mice submitted to the CUMS. The same effects were observed after an acute and subchronic nicotine administration within all examined brain structures (i.e., hippocampus, cortex, and cerebellum) and in the whole brain in non-stressed and stressed mice confirming pro-oxidative effect of nicotine. Our study contributes to the understanding of behavioral and biochemical mechanisms involved in stress-induced disorders such as depression, anxiety and memory disturbances as well as dual nicotine-stress interactions on the basis of the development of nicotine dependence.
尼古丁是烟草烟雾的主要成分，会影响情绪，并导致身体和心理依赖。考虑到尼古丁滥用与压力经常同时出现，我们旨在研究尼古丁给药与慢性不可预测轻度应激（CUMS）相结合所产生的行为和生化影响。将小鼠每天进行2小时的CUMS程序，持续4周。我们的结果显示，经历CUMS的动物在高架十字迷宫（EPM）试验中表现出类似焦虑症的行为改变，在被动回避（PA）试验中存在记忆障碍，在强迫游泳试验（FST）中出现抑郁效应。此外，急性或亚慢性给予尼古丁（0.05 - 0.5mg/kg）可减轻应激诱导的抑郁和焦虑样效应以及记忆缺陷。给予糖皮质激素拮抗剂美替拉酮（50mg/kg）可减轻CUMS诱导的抑郁效应。生化实验表明，经历CUMS的小鼠总抗氧化状态（TAS）值降低，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）活性降低，同时丙二醛（MDA）浓度升高。在所有检查的脑结构（即海马体、皮质和小脑）以及非应激和应激小鼠的全脑中，急性和亚慢性给予尼古丁后均观察到相同的效应，证实了尼古丁的促氧化作用。我们的研究有助于理解应激诱导的疾病（如抑郁、焦虑和记忆障碍）所涉及的行为和生化机制，以及基于尼古丁依赖发展的尼古丁与应激的双重相互作用。
