Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA; Experimental Research Center, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Pharmacol Biochem Behav. 2018 Dec;175:47-52. doi: 10.1016/j.pbb.2018.09.004. Epub 2018 Sep 8.
Menthol is a significant flavoring additive in tobacco products. Accumulating clinical evidence suggests that menthol may promote tobacco smoking and nicotine dependence. Our previous studies demonstrated that menthol enhanced nicotine reinforcement in rats. However, it is unclear whether menthol interacts with nicotine at the neurochemical level. The present study used intracranial microdialysis to examine whether and the ways in which menthol affects nicotine-induced dopamine release in rats in the nucleus accumbens core (NAc), a terminal field of brain reward circuitry. To make comparisons with our previous work that showed an enhancing effect of menthol on nicotine self-administration behavior, male Sprague-Dawley rats were first trained in 20 daily 1-h sessions to press a lever for intravenous nicotine self-administration (15 μg/kg/infusion). Dopamine levels were then measured in the right NAc using intracranial microdialysis coupled with high-performance liquid chromatography. Five minutes before microdialysis, the rats received an intraperitoneal injection of menthol (0, 1, 2.5, and 5 mg/kg), a subcutaneous injection of nicotine (0.2 mg/kg or its vehicle), or both. Menthol alone did not affect dopamine levels in dialysates, whereas nicotine alone elevated dopamine levels. Combined nicotine and menthol administration significantly increased dopamine levels compared with nicotine alone. These data indicate a facilitating effect of menthol on nicotine-induced dopamine release in the NAc. These findings shed light on our understanding of the neurobiological mechanisms that underlie the menthol-induced enhancement of nicotine reinforcement.
薄荷醇是烟草制品中的一种重要调味添加剂。越来越多的临床证据表明，薄荷醇可能促进吸烟和尼古丁依赖。我们之前的研究表明，薄荷醇增强了大鼠对尼古丁的强化作用。然而，薄荷醇是否在神经化学水平上与尼古丁相互作用尚不清楚。本研究使用脑室内微透析技术，检测薄荷醇是否以及以何种方式影响尼古丁诱导的大鼠伏隔核核心（NAc）中多巴胺的释放，NAc 是大脑奖励回路的一个终末场。为了与我们之前的工作进行比较，该工作表明薄荷醇增强了尼古丁的自我给药行为，首先训练雄性 Sprague-Dawley 大鼠在 20 天的 1 小时每日训练中按压杠杆进行静脉内尼古丁自我给药（15μg/kg/ 输注）。然后使用脑室内微透析与高效液相色谱法测量右侧 NAc 中的多巴胺水平。在微透析前 5 分钟，大鼠接受腹腔注射薄荷醇（0、1、2.5 和 5mg/kg）、皮下注射尼古丁（0.2mg/kg 或其载体）或两者的组合。薄荷醇单独使用不会影响透析液中的多巴胺水平，而尼古丁单独使用会升高多巴胺水平。联合给予尼古丁和薄荷醇与单独给予尼古丁相比，显著增加了多巴胺水平。这些数据表明薄荷醇对 NAc 中尼古丁诱导的多巴胺释放具有促进作用。这些发现阐明了我们对薄荷醇增强尼古丁强化作用的神经生物学机制的理解。
