Li Hui, Chen Lei, Li Peng, Wang Xiaohong, Zhai Haifeng
National Institute on Drug Dependence, Peking University, Beijing 100191, China.
School of Chinese Meteria Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
Behav Brain Res. 2014 Aug 15;270:256-60. doi: 10.1016/j.bbr.2014.05.017. Epub 2014 May 17.
Anxiety is one of the most prevalent neuropsychiatric disorders, and little is known about its pathogenesis. In order to investigate the neural mechanisms of this mental disorder, we used rat behavior in the elevated plus-maze as an animal model of anxiety and the insular cortex (insula) as a brain target. The microinjection of non-selective and selective M1 and M4 muscarinic acetylcholine receptor (mAChR) agonists or antagonists was used to explore whether the insular muscarinic receptor and its subtypes regulate levels of anxiety. The results showed that both non-selective and selective M1 and M4 mAChR agonists increased the time spent on exploring in the open arms, whereas antagonists decreased exploration. Our results indicate that activation of insular mAChRs could produce anxiolytic effects, whereas inhibition of insular mAChRs could increase anxiety. We concluded that the insular muscarinic system plays a role in the modulation of anxiety, and dysfunction of mAChR signaling may be involved in the mechanism of anxiogenesis.
焦虑是最常见的神经精神疾病之一，但其发病机制仍知之甚少。为了研究这种精神障碍的神经机制，我们将大鼠在高架十字迷宫中的行为作为焦虑动物模型，并将岛叶皮质作为脑靶点。通过微量注射非选择性、选择性M1和M4毒蕈碱型乙酰胆碱受体（mAChR）激动剂或拮抗剂，来探究岛叶毒蕈碱受体及其亚型是否调节焦虑水平。结果显示，非选择性、选择性M1和M4 mAChR激动剂均增加了在开放臂探索的时间，而拮抗剂则减少了探索行为。我们的结果表明，激活岛叶mAChRs可产生抗焦虑作用，而抑制岛叶mAChRs则会增加焦虑。我们得出结论，岛叶毒蕈碱系统在焦虑调节中发挥作用，mAChR信号功能障碍可能参与了焦虑症的发病机制。
