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Open Access Research article

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

Jin-Long Gao1, Shao-Ang Tu1, Jia Liu1, Jin-Ming Zhang2, Yiyun Huang3, Mei Han1* and Jian-Hui Liang4*

Author Affiliations

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

2 Chinese PLA General Hospital, Beijing, China

3 Yale PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA

4 Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing 100191, China

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BMC Complementary and Alternative Medicine 2014, 14:308  doi:10.1186/1472-6882-14-308

Published: 19 August 2014

Abstract

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.

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