Analytical Toxicology Laboratory, Forensic Medicine Authority, Cairo, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Neurotoxicology. 2018 Jul;67:245-258. doi: 10.1016/j.neuro.2018.06.004. Epub 2018 Jun 12.
Nicotine and tramadol concomitant drug dependence pose increasing social, economic as well as public threats. Accordingly, the present study investigated neurochemical, neurobehavioral and neuropathological changes in the brain subsequent to the interaction of nicotine and tramadol. To this end, tramadol (20 mg/kg, i.p) and nicotine (0.25 mg/kg, i.p) were administrated to male albino mice once daily for 30 days. Consequent to microglial activation, nicotine exacerbated oxidative/nitrosative stress induced by tramadol as manifest by the step-up in thiobarbituric acid reactive substances and nitric oxide subsequent to the enhanced levels of neuronal and inducible nitric oxide synthases; paralleled by decreased non-protein sulfhydryls. Increased oxidative stress by tramadol and/or nicotine sequentially augmented nuclear factor kappa B and the proinflammatory cytokine tumor necrosis factor α with the induction of apoptosis evident by the increased caspase-3 immunoreactivity. However, paradoxical to the boosted inflammation and apoptosis, heightened DA levels in the cortex parallel along with increased tyrosine hydroxylase in midbrain were apparent. Concomitant administration of tramadol and nicotine impaired spatial navigation in the Morris Water Maze test coupled with enhanced levels of acetyl- and butyryl cholinestrases. However, tramadol in association with nicotine improved social interaction while decreasing anxiety and aggression linked to chronic administration of nicotine, effects manifested by increased levels of serotonin and GABA. These results provide evidence that co-administration of tramadol and nicotine may enhance reward and dependence while reducing anxiety and aggression linked to nicotine administration. However, such combination exacerbated neurotoxic effects and elicited negative effects regarding learning and memory.
尼古丁和曲马多同时存在药物依赖会对社会、经济和公共安全造成越来越大的威胁。因此，本研究探讨了尼古丁和曲马多相互作用后大脑的神经化学、神经行为和神经病理学变化。为此，将曲马多（20mg/kg，ip）和尼古丁（0.25mg/kg，ip）每天一次给予雄性白化小鼠，共 30 天。由于小胶质细胞激活，尼古丁加剧了曲马多引起的氧化/硝化应激，表现为神经元型和诱导型一氧化氮合酶水平升高后，硫代巴比妥酸反应物质和一氧化氮增加；同时非蛋白巯基减少。曲马多和/或尼古丁引起的氧化应激依次增加核因子 kappa B 和促炎细胞因子肿瘤坏死因子 α，诱导细胞凋亡的证据是 caspase-3 免疫反应性增加。然而，与炎症和细胞凋亡的增加相反，皮质中的多巴胺水平升高与中脑酪氨酸羟化酶升高平行。曲马多和尼古丁同时给药会损害 Morris 水迷宫测试中的空间导航能力，并伴有乙酰胆碱酯酶和丁酰胆碱酯酶水平升高。然而，曲马多与尼古丁联合使用可改善慢性尼古丁给药引起的焦虑和攻击性相关的社交互动，其作用表现为血清素和 GABA 水平升高。这些结果表明，曲马多和尼古丁的联合使用可能会增强奖赏和依赖，同时降低与尼古丁给药相关的焦虑和攻击性。然而，这种组合加剧了神经毒性作用，并对学习和记忆产生了负面影响。
