These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca 2+ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.

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 Ca 2+ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine.

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 Ca 2+ influx was also examined in cultured primary neurons from E16–E18 rats.

In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus.

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.

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