Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats
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....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2019
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| Online Access: | http://psasir.upm.edu.my/id/eprint/81371/1/KRATOM.pdf |
| _version_ | 1825951429234262016 |
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| author | Hassan, Zurina Suhaimi, Farah W. Ramanathan, Surash Ling, King Hwa Effendy, Mohamad A. Muller, Christian P. Dringenberg, Hans C. |
| author_facet | Hassan, Zurina Suhaimi, Farah W. Ramanathan, Surash Ling, King Hwa Effendy, Mohamad A. Muller, Christian P. Dringenberg, Hans C. |
| author_sort | Hassan, Zurina |
| collection | UPM |
| description | 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. |
| first_indexed | 2024-03-06T10:29:53Z |
| format | Article |
| id | upm.eprints-81371 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T10:29:53Z |
| publishDate | 2019 |
| publisher | SAGE Publications |
| record_format | dspace |
| spelling | upm.eprints-813712021-06-13T01:57:06Z http://psasir.upm.edu.my/id/eprint/81371/ Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats Hassan, Zurina Suhaimi, Farah W. Ramanathan, Surash Ling, King Hwa Effendy, Mohamad A. Muller, Christian P. Dringenberg, Hans C. 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. SAGE Publications 2019 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/81371/1/KRATOM.pdf 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 https://journals.sagepub.com/doi/abs/10.1177/0269881119844186?journalCode=jopa 10.1177/0269881119844186 |
| spellingShingle | Hassan, Zurina Suhaimi, Farah W. Ramanathan, Surash Ling, King Hwa Effendy, Mohamad A. Muller, Christian P. Dringenberg, Hans C. Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats |
| title | Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats |
| title_full | Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats |
| title_fullStr | Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats |
| title_full_unstemmed | Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats |
| title_short | Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats |
| title_sort | mitragynine kratom impairs spatial learning and hippocampal synaptic transmission in rats |
| url | http://psasir.upm.edu.my/id/eprint/81371/1/KRATOM.pdf |
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