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


Hassan, Zurina and Suhaimi, Farah W. and Ramanathan, Surash and Ling, King Hwa and Effendy, Mohamad A. and Muller, Christian P. and Dringenberg, Hans C. (2019) Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats. Journal of Psychopharmacology, 33 (7). pp. 908-918. ISSN 0269-8811; ESSN: 1461-7285


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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Additional Metadata

Item Type: Article
Divisions: Faculty of Science
DOI Number: https://doi.org/10.1177/0269881119844186
Publisher: SAGE Publications
Keywords: Kratom; Mitragynine; Morris water maze; Field excitatory postsynaptic potentials; Long-term potentiation
Depositing User: Ms. Nida Hidayati Ghazali
Date Deposited: 13 Jun 2021 01:57
Last Modified: 13 Jun 2021 01:57
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1177/0269881119844186
URI: http://psasir.upm.edu.my/id/eprint/81371
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