Abuse liability of mitragynine assessed with a self-administration procedure in rats

作者：Yue, Kai; Kopajtic, Theresa A.; Katz, Jonathan L.^*

来源：Psychopharmacology, 2018, 235(10): 2823-2829.

DOI：10.1007/s00213-018-4974-9

• Mitragynine
• Kratom
• Abuse liability
• Self-administration
• Methamphetamine
• Heroin
• Medical treatments
• Opioid abuse
• Rats

Rationale Substantial use of the plant kratom for psychoactive effects has driven interest in its abuse liability. Several place conditioning studies suggest abuse liability of the active ingredient mitragynine, though studies of its self-administration have not been published.
Methods Binding of mitragynine to rat brain mu, kappa, and delta opioid receptors was compared to that for heroin and morphine. Self-administration of mitragynine, heroin, methamphetamine, or saline was assessed during single-session substitutions in rats trained to self-administer methamphetamine (0.022 mg/kg/injection, i.v.) during 1-h daily sessions.
Results Mitragynine had > 2- or similar to 16-fold greater affinity for the mu opioid receptor than, respectively, for kappa or delta opioid receptors. Its affinity for the mu receptor was similar to 200-fold less than that for morphine. In rats trained to self-administer methamphetamine, saline substitutions significantly decreased the number of responses, whereas different doses of methamphetamine (0.002-0.068 mg/kg/injection) or heroin (0.001-0.03 mg/kg/injection) maintained self-administration with maximal responding at 0.022 or 0.01 mg/kg/injection, respectively. In contrast, no dose of mitragynine maintained response rates greater than those obtained with saline. Presession mitragynine treatment (0.1 to 3.0 mg/kg) decreased response rates maintained by heroin but had little effect on responding maintained by methamphetamine across the same range of doses.
Conclusions These results suggest a limited abuse liability of mitragynine and potential for mitragynine treatment to specifically reduce opioid abuse. With the current prevalence of opioid abuse and misuse, it appears currently that mitragynine is deserving of more extensive exploration for its development or that of an analog as a medical treatment for opioid abuse.

• 出版日期2018-10
• 单位江汉大学; NIH