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Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats

Hassan Z, Suhaimi FW, Ramanathan S, Ling KH, Effendy MA, Müller CP, Dringenberg HC (2019)

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Publication Type: Journal article

Publication year: 2019

Journal

DOI: 10.1177/0269881119844186

Abstract

Background: Mitragynine is the major alkaloid of Mitragyna speciosa (Korth.) or Kratom, a psychoactive plant widely abused in Southeast Asia. While addictive effects of the substance are emerging, adverse cognitive effects of this drug and neuropharmacological actions are insufficiently understood. Aims: In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus. Methods: Male Sprague Dawley rats received daily (for 12 days) training sessions in the Morris water maze, with each session followed by treatment either with mitragynine (1, 5, or 10 mg/kg; intraperitoneally), morphine (5 mg/kg; intraperitoneally) or a vehicle. In the second experiment, we recorded field excitatory postsynaptic potentials in the hippocampal CA1 area in anesthetized rats and assessed the effects of mitragynine on baseline synaptic transmission, paired-pulse facilitation, and long-term potentiation. Gene expression of major memory- and addiction-related genes was investigated and the effects of mitragynine on Ca²⁺ influx was also examined in cultured primary neurons from E16–E18 rats. Results/outcomes: Escape latency results indicate that animals treated with mitragynine displayed a slower rate of acquisition as compared to their control counterparts. Further, mitragynine treatment significantly reduced the amplitude of baseline (i.e. non-potentiated) field excitatory postsynaptic potentials and resulted in a minor suppression of long-term potentiation in CA1. Bdnf and αCaMKII mRNA expressions in the brain were not affected and Ca²⁺ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine. Conclusions/interpretation: These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca²⁺ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.

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APA:

Hassan, Z., Suhaimi, F.W., Ramanathan, S., Ling, K.H., Effendy, M.A., Müller, C.P., & Dringenberg, H.C. (2019). Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881119844186

MLA:

Hassan, Zurina, et al. "Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats." Journal of Psychopharmacology (2019).

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