Impaired water maze learning and hippocampal long-term potentiation after mitragynine (Kratom) treatment in rats
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1
Universiti Sains Malaysia, Centre for Drug Research, Malaysia
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2
Queen's University, Department of Psychology and Centre for Neuroscience Studies, Canada
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3
Friedrich-Alexander-University of Erlangen-Nuremberg, Department of Psychiatry and Psychotherapy, Germany
Mitragynine is the major alkaloid of Mitragyna speciosa (Korth) or Kratom, a psychoactive plant consumed in Southeast Asia. The cognitive effects of this drug use are largely unknown. A methanolic extract of Mitragyna speciosa was found to inhibit the induction of long term potentiation (LTP) in hippocampal brain slices of rats. We asked whether mitragynine impairs spatial learning and long-term plasticity in the CA1 region of hippocampus in rats. Male SD rats (200-300g) were treated with mitragynine (1, 5 and 10mg/kg i.p.) and subjected to Morris water maze or electrophysiological recordings (under urethane anesthesia) to assess the changes in long-term plasticity of hippocampal synapses. Rats treated with mitragynine (5 and 10mg/kg i.p.) showed slower acquisition of the escape to the hidden platform over 12 days of training, as well as a reduction of time spent in the target quadrant of the maze (p < 0.05). In urethane-anesthetized rats, delivery of either a weaker and strong theta-burst stimulation (TBS) resulted in about 50% and 100% potentiation, respectively, of field excitatory postsynaptic potentials (fEPSP) recorded in the hippocampal CA1 area. Mitragynine treatment resulted in a significant (p < 0.05) suppression of LTP induced with the strong induction protocol. Interestingly, mitragynine (10 mg/kg, i.p.) also reduced (to about 54%) the amplitude of baseline (i.e., non-potentiated) fEPSP in CA1. These data show that mitragynine impairs spatial learning, suppresses baseline transmission at CA3 –CA1 synapses, and inhibits LTP in CA1 neurons. Thus, hippocampal dysfunction may constitute an important, contributing factor to the cognitive and behavioural deficits in mitragynine-treated rats.
Acknowledgements
Higher Education Centre of Excellence (HICoE) special funding (304.CDADAH.650527.K134) and International Research Collaboration Fund (IReC) (1002.CDADAH.910410)
Keywords:
Hippocampus,
Long-Term Potentiation,
neuroplasticity,
mitragynine,
CA1 neurons
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
YIC02: Young Investigator Colloquium 2
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Hassan
Z,
Suhaimi
F,
Dringenberg
HC and
Muller
CP
(2016). Impaired water maze learning and hippocampal long-term potentiation after mitragynine (Kratom) treatment in rats.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00058
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Received:
04 Aug 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Dr. Zurina Hassan, Universiti Sains Malaysia, Centre for Drug Research, Minden, Penang, Malaysia, zurina_hassan@hotmail.com