Related Experiment Video
Updated: Jul 11, 2025
Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents
Published on: September 4, 2015
Mitragynine inhibits hippocampus neuroplasticity and its molecular mechanism
Suleiman Yunusa1,2, Zurina Hassan3, Christian P Müller4,5,6,7
1Centre for Drug Research, Universiti Sains Malaysia, 11800, Penang, Malaysia.
Background:
Mitragynine (MIT), the primary indole alkaloid of kratom (Mitragyna speciosa), has been associated with addictive and cognitive decline potentials. In acute studies, MIT decreases spatial memory and inhibits hippocampal synaptic transmission in long-term potentiation (LTP). This study investigated the impacts of 14-day MIT treatment on hippocampus synaptic transmission and its possible underlying mechanisms.
Methods:
Under urethane anesthesia, field excitatory post-synaptic potentials (fEPSP) of the hippocampal CA1 region were recorded in the Sprague Dawley (SD) rats that received MIT (1, 5, and 10 mg/kg), morphine (MOR) 5 mg/kg, or vehicle (ip). The effects of the treatments on basal synaptic transmission, paired-pulse facilitation (PPF), and LTP were assessed in the CA1 region. Analysis of the brain's protein expression linked to neuroplasticity was then performed using a western blot.
Results:
The baseline synaptic transmission's amplitude was drastically decreased by MIT at 5 and 10 mg/kg doses, although the PPF ratio before TBS remained unchanged, the PPF ratio after TBS was significantly reduced by MIT (10 mg/kg). Strong and persistent inhibition of LTP was generated in the CA1 region by MIT (5 and 10 mg/kg) doses; this effect was not seen in MIT (1 mg/kg) treated rats. In contrast to MIT (1 mg/kg), MIT (5 and 10 mg/kg) significantly raised the extracellular glutamate levels. After exposure to MIT, GluR-1 receptor expression remained unaltered. However, NMDAε2 receptor expression was markedly downregulated. The expression of pCaMKII, pERK, pCREB, BDNF, synaptophysin, PSD-95, Delta fosB, and CDK-5 was significantly downregulated in response to MIT (5 and 10 mg/kg) exposure, while MOR (5 mg/kg) significantly raised synaptophysin and Delta fosB expression.
Conclusion:
Findings from this work reveal that a smaller dose of MIT (1 mg/kg) poses no risk to hippocampal synaptic transmission. Alteration in neuroplasticity-associated proteins may be a molecular mechanism for MIT (5 and 10 mg/kg)-induced LTP disruption and cognitive impairments. Data from this work posit that MIT acted differently from MOR on neuroplasticity and its underlying mechanisms.
Insights
Mitragynine (MIT) at higher doses impairs hippocampal synaptic transmission and long-term potentiation (LTP) in rats by altering neuroplasticity proteins. Lower MIT doses (1 mg/kg) did not affect synaptic function, suggesting a dose-dependent effect.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Mitragynine (MIT), the main alkaloid in kratom, is linked to addiction and cognitive deficits.
- Previous studies show MIT impairs spatial memory and hippocampal synaptic transmission, specifically long-term potentiation (LTP).
- This study investigates the chronic effects of MIT on hippocampal synaptic transmission and its molecular mechanisms.
Purpose of the Study:
- To determine the impact of 14-day MIT treatment on hippocampal CA1 synaptic transmission and LTP.
- To elucidate the underlying molecular mechanisms, focusing on neuroplasticity-related protein expression.
Main Methods:
- Electrophysiological recordings of field excitatory post-synaptic potentials (fEPSPs) in the hippocampal CA1 region of Sprague Dawley rats.
- Assessment of basal synaptic transmission, paired-pulse facilitation (PPF), and LTP following administration of MIT (1, 5, 10 mg/kg), morphine (5 mg/kg), or vehicle.
- Western blot analysis of neuroplasticity-associated proteins, including GluR-1, NMDAε2, pCaMKII, pERK, pCREB, BDNF, synaptophysin, PSD-95, Delta fosB, and CDK-5.
Main Results:
- MIT (5 and 10 mg/kg) significantly reduced baseline synaptic transmission amplitude and inhibited LTP.
- MIT (10 mg/kg) reduced the PPF ratio post-theta burst stimulation (TBS), while MIT (5 and 10 mg/kg) increased extracellular glutamate levels.
- MIT (5 and 10 mg/kg) downregulated NMDAε2 receptor expression and key neuroplasticity proteins (pCaMKII, pERK, pCREB, BDNF, synaptophysin, PSD-95, Delta fosB, CDK-5), unlike lower MIT doses or morphine.
Conclusions:
- Low-dose MIT (1 mg/kg) does not pose a risk to hippocampal synaptic transmission or LTP.
- Higher MIT doses (5 and 10 mg/kg) disrupt hippocampal synaptic transmission and LTP, likely through downregulation of neuroplasticity-associated proteins.
- MIT affects neuroplasticity through distinct mechanisms compared to morphine.
More Related Videos
14:57Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
09:51Recording Synaptic Plasticity in Acute Hippocampal Slices Maintained in a Small-volume Recycling-, Perfusion-, and Submersion-type Chamber System
Published on: January 1, 2018
