Discriminative stimulus properties of mitragynine (kratom) in rats

Rationale Mitragynine (MG) is the primary active alkaloid extracted from the leaves of Mitragyna speciosa or kratom and exhibits pharmacological activities mediated by opioid receptors. The plant has been traditionally used for its opium and psychostimulant-like effects to increase work efficiency or as a substitute in the self-treatment of opiate addiction. Objectives The present study was performed to investigate the discriminative stimulus effects of MG in rats. The pharmacological mechanism of MG action and its derivative, 7-hydroxymitragynine (7-HMG) with a specific focus on opioid receptor involvement was examined in rats trained to discriminate morphine from vehicle. In order to study the dual actions of MG, the effect of cocaine substitution to the MG discriminative stimulus was also performed in MG-trained rats. Methods Male Sprague Dawley rats were trained to discriminate MG from vehicle in a two-lever drug discrimination procedure under a tandem variable-interval (VI 60') fixed-ratio (FR 10) schedule of food reinforcement. Results Rats acquired the MG discrimination (15.0 mg/kg, i.p.) which was similar to the acquisition of morphine discrimination (5.0 mg/kg, i.p.) in another group of rats. MG substituted fully to the morphine discriminative stimulus in a dose-dependent manner, suggesting pharmacological similarities between the two drugs. The administration of 7-HMG derivative in 3.0 mg/kg (i.p.) dose engendered full generalisation to the morphine discriminative stimulus. In addition, the MG stimulus also partially generalised to cocaine (10.0 mg/kg, i.p.) stimulus. Conclusion The present study demonstrates that the discriminative stimulus effect of MG possesses both opioid-and psychostimulant-like subjective effects.