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Mitragynine, a primary constituent of kratom reinstates morphine-seeking behaviour in rats

Lookup NU author(s): Dr Mohammed Shoaib

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Abstract

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.

Publication metadata

Author(s): Japarin RA, Harun N, Hassan Z, Shoaib M

Publication type: Article

Publication status: Published

Journal: Behavioural Pharmacology

Year: 2023

Volume: 34

Issue: 2-3

Pages: 123-130

Print publication date: 01/04/2023

Online publication date: 21/12/2022

Acceptance date: 02/04/2022

ISSN (print): 0955-8810

ISSN (electronic): 1473-5849

Publisher: Lippincott Williams and Wilkins

URL: https://doi.org/10.1097/FBP.0000000000000715

DOI: 10.1097/FBP.0000000000000715

PubMed id: 36752325

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