Oleanolic Acid Attenuates Morphine Withdrawal Symptoms in Rodents: Association with Regulation of Dopamine Function

Abstract

Introduction

Oleanolic acid (OA) has been shown to be useful for the treatment of mental disorders.

Methods

In this study, we investigated the effects of OA in animal models of spontaneous withdrawal and naloxone-precipitated withdrawal and evaluated the effects of OA on the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP).

Results

OA significantly improved symptoms of withdrawal, and significantly reduced the acquisition and reinstatement of morphine-induced conditioned place preference. Moreover, OA significantly reduced the serum content of 5-hydroxy tryptamine (5-HT) and dopamine (DA) in a dose-dependent manner, and reduced norepinephrine (NE) and 5-HT content in the frontal cortex (PFC), while significantly increasing endorphin content in rats. OA also significantly reduced serum DA content in mice.

Conclusion

These results indicate that OA can improve the withdrawal symptoms of rats and mice by regulating the DA system and suggest that OA may be useful in treatment of morphine addiction.

Keywords:

• OA
• withdrawal
• morphine-induced
• rats
• mice

Acknowledgments

The authors would like to express their gratitude to EditSprings for the expert linguistic services provided.

Data Sharing Statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Ethics Approval and Consent to Participate

The study was carried out in compliance with the ARRIVE guidelines. The animal protocol was reviewed and approved by the Ethical Committee Acts of Guangdong Provincial Institute of Traditional Chinese Medicine (No. SYXK2020-0059). All methods were carried out in accordance with the Guangdong Province Laboratory Animal Care and Use Guidelines.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare.

Additional information

Funding

This project was supported by the Natural Science Foundation from education department of Jiangsu Province, China (Grant Number: 19KJB360001) and Changzhou Science and Technology and Information Bureau (Grant Number: CJ20189003 and CJ20190011).