Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, United States.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, United States.
Eur J Pharmacol. 2019 Oct 15;861:172592. doi: 10.1016/j.ejphar.2019.172592. Epub 2019 Aug 14.
Neurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is an NMDA glutamate antagonist used to improve cognitive function in people with Alzheimer's disease. Glutamate may be an important component of the reinforcing effects of nicotine, so memantine was evaluated as a potential smoking cessation aid. Two studies were conducted with adult female rats, one testing acute effects of memantine over a range of doses for changing nicotine self-administration and the other testing the chronic effects of memantine to reduce nicotine self-administration. Acute memantine injections slightly, but significantly, increased nicotine self-administration in a dose-related manner. In contrast, chronic memantine treatment significantly reduced nicotine self-administration. During the first day of memantine administration in the chronic study, nicotine self-administration was significantly elevated replicating the acute study. Starting in the second week of treatment there was a significant reduction of nicotine self-administration relative to controls. This was seen because memantine treatment prevented the increase in nicotine self-administration shown by controls. There even continued to be a memantine-induced lowered nicotine self-administration during the week after the cessation of memantine treatment. Memantine or other drugs affecting NMDA glutamate receptors may be useful aids to smoking cessation. Full efficacy for reducing nicotine self-administration was seen as the NMDA drug treatment is given chronically. Importantly, the effect persisted even after treatment is ended, indicating the high potential for NMDA glutamate receptors to impact nicotine addiction.
神经行为基础的烟草成瘾和尼古丁强化是复杂的，涉及到不仅仅是烟碱型乙酰胆碱能或多巴胺能系统。美金刚是一种 NMDA 谷氨酸拮抗剂，用于改善阿尔茨海默病患者的认知功能。谷氨酸可能是尼古丁强化作用的一个重要组成部分，所以美金刚被评估为一种潜在的戒烟辅助药物。两项研究使用成年雌性大鼠进行，一项研究测试美金刚在一系列剂量下对改变尼古丁自我给药的急性作用，另一项研究测试美金刚的慢性作用，以减少尼古丁自我给药。急性美金刚注射以剂量相关的方式轻微但显著地增加了尼古丁的自我给药。相比之下，慢性美金刚治疗显著减少了尼古丁的自我给药。在慢性研究中美金刚给药的第一天，尼古丁的自我给药显著升高，复制了急性研究的结果。从治疗的第二周开始，与对照组相比，尼古丁的自我给药有显著减少。这是因为美金刚治疗阻止了对照组中尼古丁自我给药的增加。即使在停止美金刚治疗后的一周内，仍继续存在美金刚诱导的降低尼古丁自我给药。美金刚或其他影响 NMDA 谷氨酸受体的药物可能是戒烟的有用辅助药物。减少尼古丁自我给药的完全疗效是作为 NMDA 药物治疗慢性给予的。重要的是，即使治疗结束后，这种效果仍然持续，表明 NMDA 谷氨酸受体对尼古丁成瘾的影响潜力很大。
