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Evidence for intravenous self-administration of mitragynine in fentanyl-dependent rats

Lookup NU author(s): Norazam Harun, Dr Mohammed Shoaib


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© 2021, Faculty of Pharmaceutical Sciences, Chulalongkorn University. All rights reserved.Introduction: Kratom (Mitragyna speciosa Korth) is currently used as an alternative for the self-treatment of pain and management of opioid dependence and withdrawal. Due to the opioid-like effect of the plant’s active alkaloid, mitragynine (MG), the evaluation of its ability to maintain self-administration in animal models of opioid dependence appears to be great significance. Objectives: Here, the ability of MG to cross-substitute to the reinforcing effects of the synthetic narcotic fentanyl is investigated. Methods: Rats with implanted catheters were allowed to self-administer fentanyl (2.0 μg/kg/infusion) on a fixed-ratio 1 of schedule of reinforcement. Results: A significant increase in lever pressing indicated the successful acquisition of fentanyl self-administration. Next, rats were presented with saline or various doses of MG. The cross-substitution of MG at three unit doses (0.3, 1.0, and 3.0 mg/kg/infusion) maintained the lever-pressing responses of the fentanyl self-administration while extinction was evident following the substitution of saline for the fentanyl solution. Conclusion: The differences in the profile of MG cross-substitution tests to the baseline level observed during extinction suggest that MG has fentanyl-like reinforcing effects. However, a more thorough examination of its primary reinforcing effects will need to be determined in naïve rats to confirm the potential dependence producing effects of MG.

Publication metadata

Author(s): Harun N, Hassan Z, Ramanathan S, Shoaib M

Publication type: Article

Publication status: Published

Journal: Thai Journal of Pharmaceutical Sciences

Year: 2021

Volume: 45

Issue: 4

Pages: 242-247

Online publication date: 08/03/2021

Acceptance date: 01/02/2021

ISSN (print): 0125-4685

ISSN (electronic): 1905-4637

Publisher: Faculty of Pharmaceutical Sciences, Chulalongkorn University