Li Yongfeng, Zhu Jianyu, Zheng Qiaohua, Qian Zhaoqiang, Zhang Lizi, Wei Chunling, Han Jing, Liu Zhiqiang, Ren Wei
MOE Key Laboratory of Modern Teaching Technology, Center for Teacher Professional Ability Development, Shaanxi Normal University, Xi'an.
Institutes of Brain Science, Fudan University, Shanghai, China.
Neuroreport. 2019 Jun 12;30(9):681-687. doi: 10.1097/WNR.0000000000001260.
Chronic stress, including chronic neuropathic pain, cannot only induce depressive disorders but also enhance sensitization to addictive drugs. Ample evidence support the implication of the 5-hydroxytryptamine (5-HT) system in the enhanced sensitization to cocaine. However, mechanisms underpinning such an enhancement are still unclear. By using a neuropathic pain model and a combination of behavioral, neurochemical, and western blotting techniques, this study reveals that the mice experienced with chronic neuropathic pain express both depression-like disorders and significant conditioned place preference to cocaine. The conditioned place preference to cocaine and was abolished by administration of the 5-HT1A receptor antagonist into the dorsal raphe nucleus (DRN). The expression of DRN 5-HT1A receptor was upregulated in mice experienced with chronic neuropathic pain. Moreover, such an upregulation was restored by repeated exposure to cocaine. The results reveal that DRN 5-HT1A receptor mediate the sensitization to cocaine in mice experienced with chronic pain and may be used as a new molecular target for therapeutic interventions to drug addiction influenced by chronic stress.
慢性应激，包括慢性神经性疼痛，不仅会诱发抑郁症，还会增强对成瘾药物的敏感性。大量证据支持5-羟色胺（5-HT）系统与对可卡因敏感性增强有关。然而，这种增强作用的潜在机制仍不清楚。通过使用神经性疼痛模型以及行为学、神经化学和蛋白质印迹技术相结合的方法，本研究发现经历慢性神经性疼痛的小鼠既表现出类似抑郁的症状，又对可卡因有显著的条件性位置偏爱。向背侧中缝核（DRN）注射5-HT1A受体拮抗剂可消除对可卡因的条件性位置偏爱。在经历慢性神经性疼痛的小鼠中，DRN 5-HT1A受体的表达上调。此外，反复接触可卡因可使这种上调恢复。结果表明，DRN 5-HT1A受体介导了慢性疼痛小鼠对可卡因的敏感性，可能作为治疗受慢性应激影响的药物成瘾的新分子靶点。
