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

Hassan Z 1 , Suhaimi FW 1 , Ramanathan S 1 , Ling KH 2 , Effendy MA 1 , Müller CP 3 Show all authors , Dringenberg HC 4

Affiliations 

  • 1 1 Centre for Drug Research, Universiti Sains Malaysia, Penang, Malaysia
  • 2 2 Department of Biomedical Science, Universiti Putra Malaysia, Selangor, Malaysia
  • 3 3 Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany
  • 4 4 Department of Psychology and Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada
J. Psychopharmacol. (Oxford), 2019 07;33(7):908-918.
PMID: 31081443 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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