Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, Key Laboratory for Neuroscience of the Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, Key Laboratory for Neuroscience of the Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
Neuroscience. 2018 Dec 1;394:164-176. doi: 10.1016/j.neuroscience.2018.10.032. Epub 2018 Oct 24.
Anxiety is considered an important protracted abstinence symptom that can aggravate craving and relapse risk in opioid addicts. Although the insular cortex (IC) has been reported to be a key brain region in mediating emotional and motivational alterations induced by drug consumption and withdrawal, the role of IC in anxiety related to protracted abstinence remains elusive. In this study, we found that: (1) anxiety-like behavior in morphine-dependent mice became significant after 28 days of withdrawal, while their physical symptoms became undetectable. (2) Activated glutamatergic neurons in the medial IC, but not the anterior or posterior IC were significantly increased after 28 days of withdrawal. Bilateral lesion of the medial IC, but not the anterior or posterior IC with ibotenic acid (IBO) alleviated the anxiety-like behavior. (3) Expression of Wnt7a in the medial IC was significantly increased after 28 days of withdrawal, and specific down-regulation of Wnt7a with AAV-shWnt7a also alleviated the anxiety-like behavior. The findings reveal the medial IC is involved in mediating anxiety-like behavior related to morphine protracted abstinence, in which Wnt7a plays a critical role.
焦虑被认为是阿片类药物成瘾者戒断后重要的迁延性戒断症状，可加重成瘾者的觅药欲望和复吸风险。尽管有研究报道岛叶皮层（Insular Cortex，IC）在介导药物使用和戒断引起的情绪和动机改变中是关键脑区，但 IC 在迁延性戒断相关焦虑中的作用仍不清楚。在这项研究中，我们发现：（1）吗啡依赖小鼠在戒断 28 天后出现明显的焦虑样行为，而其躯体戒断症状则检测不到；（2）戒断 28 天后，内侧 IC 的谷氨酸能神经元被激活，而前侧和后侧 IC 则没有明显变化。内侧 IC 的双侧损毁（而非前侧或后侧 IC 的损毁），用 IBX 缓解了焦虑样行为；（3）戒断 28 天后，内侧 IC 中的 Wnt7a 表达明显增加，用 AAV-shWnt7a 特异性下调 Wnt7a 也缓解了焦虑样行为。研究结果表明，内侧 IC 参与介导吗啡迁延性戒断相关的焦虑样行为，其中 Wnt7a 发挥关键作用。
