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中药济泰片对吗啡依赖大鼠自然戒断症状及多巴胺能功能调节的影响

Effects of Jitai tablet, a traditional Chinese medicine, on spontaneous withdrawal symptoms and modulation of dopaminergic functions in morphine-dependent rats.

作者信息

Tu Shaoang, Gao Jinlong, Liu Jia, Zhang Jinming, Huang Yiyun, Xu Shasha, Han Mei, Liang Jianhui

机构信息

Key Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing, 100875, China.

出版信息

Phytother Res. 2015 May;29(5):687-94. doi: 10.1002/ptr.5300. Epub 2015 Jan 27.

Abstract

Chronic opioid abuse can cause damage to dopamine neurons. However, there are currently no effective pharmacotherapies to reverse this damage, even though progress has been made in the development of therapeutic strategies for opioid dependence. The Jitai tablet (JTT) is a traditional Chinese medicine formulation most commonly used for opioid addiction treatment in China. In a morphine spontaneous withdrawal rat model we investigated the effects of JTT, either given before (pre-treatment) or after (post-treatment) morphine administration, on the dopamine system. Our study has shown the following: (1) pre- and post-treatment with JTT were effective at alleviating the wet dog shakes and episodes of writhing; (2) pre-treatment with JTT inhibited the morphine-induced decreases in dopamine transporter (DAT), dopamine D2 receptor (D2 R) and tyrosine hydroxylase (TH) levels in the striatum (p < 0.01, compared with morphine group) and maintained them at normal levels; and (3) post-treatment with JTT restored the densities of DAT, D2 R and TH in the striatum to normal levels (p < 0.01, compared with morphine group). These results support the notion that modulation of the dopamine system in the striatum may play a role for JTT's therapeutic effect on the alleviation of opioid withdrawal symptoms.

摘要

长期阿片类药物滥用会导致多巴胺神经元受损。然而,尽管在阿片类药物依赖治疗策略的开发方面已取得进展,但目前尚无有效的药物疗法来逆转这种损伤。济泰片(JTT)是中国最常用于治疗阿片类药物成瘾的一种中药制剂。在吗啡自发戒断大鼠模型中,我们研究了在吗啡给药之前(预处理)或之后(后处理)给予JTT对多巴胺系统的影响。我们的研究结果如下:(1)JTT预处理和后处理均能有效减轻湿狗样抖动和扭体发作;(2)JTT预处理可抑制吗啡诱导的纹状体中多巴胺转运体(DAT)、多巴胺D2受体(D2R)和酪氨酸羟化酶(TH)水平降低(与吗啡组相比,p < 0.01),并使其维持在正常水平;(3)JTT后处理可使纹状体中DAT、D2R和TH的密度恢复至正常水平(与吗啡组相比,p < 0.01)。这些结果支持这样一种观点,即调节纹状体中的多巴胺系统可能在JTT缓解阿片类药物戒断症状的治疗效果中发挥作用。

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