An-jun-ning, a traditional herbal formula, attenuates spontaneous withdrawal symptoms via modulation of the dopamine system in morphine-dependent rats

BMC Complementary and Alternative Medicine

Jian-Hui Liang²  Mei Han¹  Yiyun Huang³  Jin-Ming Zhang⁴  Jia Liu¹  Shao-Ang Tu¹  Jin-Long Gao¹ 

[1] Key Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing 100875, China;Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing 100191, China;Yale PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA;Chinese PLA General Hospital, Beijing, China

关键词: An-jun-ning;    Tyrosine hydroxylase;    Dopamine D₂receptor;    Dopamine transporter;    Morphine dependence;   

Others  :  1086919
DOI  :  10.1186/1472-6882-14-308

 received in 2013-11-12, accepted in 2014-07-16,  发布年份 2014

【 摘 要 】

Background

The dopamine system, which is involved in drug dependence, can be damaged by opioid abuse. However, current clinical medicines cannot reverse these damages in the brain, which are believed to be a key reason for the high relapse rate after abstinence treatment. This study aimed to investigate the effects of An-jun-ning (AJN), a commercial traditional Chinese medicine formula used for the treatment of opioid addiction, on the dopamine system in morphine-dependent rats and to explore the possible mechanism underlying its therapeutic effects.

Methods

The morphine dependence model was obtained through injections of morphine at increasing doses for 8 days. The AJN pre-treatment group was administered AJN 30 min before each morphine administration, and the AJN post-treatment groups were treated with AJN for 10 days after withdrawal. Spontaneous withdrawal symptoms (wet dog shakes, and episodes of writhing) were observed after withdrawal. Autoradiography study and/or immunohistochemical staining were used to examine the levels of dopamine transporter (DAT), dopamine D₂ receptor (D₂R) and tyrosine hydroxylase (TH).

Results

(1) Pre-treatment with AJN attenuates wet dog shakes and episodes of writhing to approximately 50% or less of those observed in the morphine group (p < 0.01). (2) AJN post-treatment dose-dependently reduced the number of wet dog shakes (p < 0.01), and the episodes of writhing (p < 0.01). (3) Pre-treatment with AJN effectively interdicted the morphine-induced decreases in the levels of DAT, D₂R, and TH in the striatum (p < 0.01) such that they remained at nearly normal levels. (4) Post-treatment with AJN restored DAT and D₂R to the normal levels (p < 0.01) and the level of TH to 87% of normal in the striatum.

Conclusions

AJN can effectively alleviate opioid withdrawal symptoms and preserve or restore the DAT, D₂R, and TH levels in the striatum. The mechanism underlying the effect of AJN on withdrawal symptoms may be related to the modulation of the dopamine system by AJN. These results suggest that AJN may help to prevent relapse in opioid dependence treatment.

【 授权许可】

   
2014 Gao et al.; licensee BioMed Central Ltd.

【 图 表 】

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