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

Zhiqi Shi,1,2 Shugang Pan,3,4 Luolin Wang,5 Sha Li2 1School of Pharmacy, Changzhou Institute of Industry and Technology, Changzhou, Jiangsu, People’s Republic of China; 2Longsha Medical Research Institute, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, People’s Republic of China; 3School of Pharmacy, Changzhou Institute of Technology, Changzhou, 213022, People’s Republic of China; 4Key Laboratory for Soft Chemistry and Functional Materials of Ministry Education, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 5Department of Pharmacy, Guangdong Provincial Institute of Traditional Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Zhiqi ShiSchool of Pharmacy, Changzhou Institute of Industry and Technology, No. 28#, Mingxin Road, Changzhou, Jiangsu Province, 213164, People’s Republic of ChinaTel +86 519-86335118Email shi_mars@foxmail.comSha LiLongsha Medical Research Institute, Wuxi Hospital of Traditional Chinese Medicine, No. 8#, Zhongnan Road, Wuxi, Jiangsu Province, 214071, People’s Republic of ChinaTel +86 510-88859999Email sl0426@foxmail.comIntroduction: 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, mic