Abstract
BackgroundThe 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.MethodsThe 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.ConclusionsAJN 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.
Highlights
The dopamine system, which is involved in drug dependence, can be damaged by opioid abuse
These results suggest that AJN may help to prevent relapse in opioid dependence treatment
This study provides the first preclinical investigation on the modulation of the dopamine system as a mechanism underlying the therapeutic action of the traditional Chinese medicine formula An-jun-ning in alleviating spontaneous withdrawal symptoms in opioid dependence
Summary
The dopamine system, which is involved in drug dependence, can be damaged by opioid abuse. It has been reported that approximately 50% of patients experienced relapse behavior within a few days after completing treatment in a hospital [2] Another follow-up investigation found that even when presenting to buprenorphine treatment, youth with opioid use within the past 30 days were less likely to avoid relapse at week 12 of treatment [3]. There are some first-line medicines for the treatment of opioid addiction that effectively alleviate the opioid withdrawal symptoms. These include methadone, buprenorphine, naloxone, naltrexone, lofexidine and clonidine. Most of these drugs have undesirable side effects, such as abuse potential and high relapse rate and cannot effectively reverse the adaptive neurobiological changes. More effective and safer approaches for the treatment of opioid addiction are urgently needed
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