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      Drug Design, Development and Therapy (submit here)

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      Is Open Access

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


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


          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).


          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.


          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.

          Most cited references59

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          The neural basis of addiction: a pathology of motivation and choice.

          A primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. In this review the authors explore how advances in neurobiology are approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding. Findings from neuroimaging of addicts are integrated with cellular studies in animal models of drug seeking. While dopamine is critical for acute reward and initiation of addiction, end-stage addiction results primarily from cellular adaptations in anterior cingulate and orbitofrontal glutamatergic projections to the nucleus accumbens. Pathophysiological plasticity in excitatory transmission reduces the capacity of the prefrontal cortex to initiate behaviors in response to biological rewards and to provide executive control over drug seeking. Simultaneously, the prefrontal cortex is hyperresponsive to stimuli predicting drug availability, resulting in supraphysiological glutamatergic drive in the nucleus accumbens, where excitatory synapses have a reduced capacity to regulate neurotransmission. Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control (choice), and enhancing glutamatergic drive in response to drug-associated stimuli.
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            Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

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              Pharmacology of oleanolic acid and ursolic acid.

              Jie Liu (1995)
              Oleanolic acid and ursolic acid are triterpenoid compounds that exist widely in food, medicinal herbs and other plants. This review summarizes the pharmacological studies on these two triterpenoids. Both oleanolic acid and ursolic acid are effective in protecting against chemically induced liver injury in laboratory animals. Oleanolic acid has been marketed in China as an oral drug for human liver disorders. The mechanism of hepatoprotection by these two compounds may involve the inhibition of toxicant activation and the enhancement of the body defense systems. Oleanolic acid and ursolic acid have also been long-recognized to have antiinflammatory and antihyperlipidemic properties in laboratory animals, and more research is warranted to develop a therapy for patients. Recently, both compounds have been noted for their antitumor-promotion effects, which are stimulating additional research in this field. Oleanolic acid and ursolic acid are relatively non-toxic, and have been used in cosmetics and health products. The possible mechanisms for the pharmacological effects and the prospects for these two compounds are discussed.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                24 August 2021
                : 15
                : 3685-3696
                [1 ]School of Pharmacy, Changzhou Institute of Industry and Technology , Changzhou, Jiangsu, People’s Republic of China
                [2 ]Longsha Medical Research Institute, Wuxi Hospital of Traditional Chinese Medicine , Wuxi, Jiangsu, People’s Republic of China
                [3 ]School of Pharmacy, Changzhou Institute of Technology , Changzhou, 213022, People’s Republic of China
                [4 ]Key Laboratory for Soft Chemistry and Functional Materials of Ministry Education, Nanjing University of Science and Technology , Nanjing, People’s Republic of China
                [5 ]Department of Pharmacy, Guangdong Provincial Institute of Traditional Chinese Medicine , Guangzhou, People’s Republic of China
                Author notes
                Correspondence: Zhiqi Shi School of Pharmacy, Changzhou Institute of Industry and Technology , No. 28#, Mingxin Road, Changzhou, Jiangsu Province, 213164, People’s Republic of ChinaTel +86 519-86335118 Email shi_mars@foxmail.com
                Sha Li Longsha Medical Research Institute, Wuxi Hospital of Traditional Chinese Medicine , No. 8#, Zhongnan Road, Wuxi, Jiangsu Province, 214071, People’s Republic of ChinaTel +86 510-88859999 Email sl0426@foxmail.com
                Author information
                © 2021 Shi et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 25 June 2021
                : 09 August 2021
                Page count
                Figures: 8, Tables: 6, References: 59, Pages: 12
                Funded by: Natural Science Foundation from education department of Jiangsu Province, China;
                Funded by: Changzhou Science and Technology and Information Bureau;
                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).
                Original Research

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine
                oa, withdrawal, morphine-induced, rats, mice


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