Bade Aditya N, Gendelman Howard E, Boska Michael D, Liu Yutong
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Omaha 68198-5880, NE, United States.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical CenterOmaha 68198-5880, NE, United States; Department of Radiology, University of Nebraska Medical CenterOmaha 68198-5880, NE, United States.
Am J Transl Res. 2017 Feb 15;9(2):601-610. eCollection 2017.
Nicotine dependence is defined by dopaminergic neuronal activation within the nucleus accumbens (ACB) and by affected neural projections from nicotine-stimulated neurons. Control of any subsequent neural activities would underpin any smoking cessation strategy. While extensive efforts have been made to study the pathophysiology of nicotine addiction, more limited works were developed to find imaging biomarkers. If such biomarkers are made available, addictive behaviors could be monitored noninvasively. To such ends, we employed manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) to determine whether it could be used to monitor neuronal activities after acute and chronic nicotine exposure in rats. The following were observed. Mn infusion identified ACB and hippocampal (HIP) neuronal activities following acute nicotine administration. Chronic exposure was achieved by week long subcutaneously implanted nicotine mini-pump. Here nicotine was shown to activate neurons in the ACB, HIP, and the prefrontal and insular cortex. These are all central nervous system reward regions linked to drug addiction. In conclusion, MEMRI is demonstrated to be a powerful imaging tool to study brain subregion specific neuronal activities affected by nicotine. Thus, we posit that MEMRI could be used to assess smoking-associated tolerance, withdrawal and as such serve as a pre-clinical screening tool for addiction cessation strategies in humans.
尼古丁依赖由伏隔核（ACB）内的多巴胺能神经元激活以及尼古丁刺激神经元的神经投射受影响来定义。控制任何后续的神经活动将是任何戒烟策略的基础。虽然已经付出巨大努力来研究尼古丁成瘾的病理生理学，但开发用于寻找成像生物标志物的工作却较为有限。如果能够获得此类生物标志物，就可以对成瘾行为进行无创监测。为此，我们采用锰（Mn）增强磁共振成像（MEMRI）来确定其是否可用于监测大鼠急性和慢性尼古丁暴露后的神经元活动。观察到以下情况。锰注入可识别急性尼古丁给药后伏隔核和海马体（HIP）的神经元活动。通过皮下植入尼古丁微型泵持续一周来实现慢性暴露。结果显示，尼古丁可激活伏隔核、海马体以及前额叶和岛叶皮质中的神经元。这些都是与药物成瘾相关的中枢神经系统奖赏区域。总之，MEMRI被证明是一种强大的成像工具，可用于研究受尼古丁影响的脑亚区特定神经元活动。因此，我们认为MEMRI可用于评估与吸烟相关的耐受性、戒断反应，从而作为人类成瘾戒断策略的临床前筛查工具。
