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Related Experiment Videos

MPTP and convulsive responses in rodents.

R G Fariello1, M DeMattei, M Castorina

  • 1Department of Neurology, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107.

Brain Research
|November 24, 1987
PubMed
Summary

MPTP administration abolished strychnine and maximal electroshock seizures in mice by affecting hindbrain structures. Dopamine depletion correlated with seizure resistance, suggesting a protective role.

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Area of Science:

  • Neuroscience
  • Neuropharmacology
  • Neurotoxicology

Background:

  • The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause dopamine depletion.
  • Seizure mechanisms and the brain regions involved are not fully elucidated, particularly concerning hindbrain structures.

Purpose of the Study:

  • To investigate the effects of MPTP on various seizure models in mice.
  • To explore the potential role of MPTP-induced neurochemical changes in seizure modulation.
  • To identify the brain pathways involved in MPTP-induced anticonvulsant effects.

Main Methods:

  • Mice were administered MPTP (30 mg/kg s.c. for 5 days).
  • Seizure susceptibility was assessed using strychnine, maximal electroshock, bicuculline, picrotoxin, and pentylenetetrazole.

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  • Neurochemical analysis of dopamine and norepinephrine levels in the striatum and hippocampus was performed.
  • Histological examination of the substantia nigra was conducted.

    • Main Results:

    • MPTP administration completely abolished strychnine-induced seizures and the tonic phase of maximal electroshock responses.
    • MPTP treatment mildly but significantly reduced the severity of pentylenetetrazole-induced seizures.
    • Bicuculline and picrotoxin convulsions were not significantly affected.
    • MPTP depleted neostriatal dopamine and its metabolites, and hippocampal norepinephrine, without causing nigral neuronal loss.

    Conclusions:

    • Strychnine seizures and maximal electroshock responses involve hindbrain (bulbo-spinal) structures.
    • MPTP induces resistance to certain seizures, suggesting a caudally projecting system from the substantia nigra and/or locus coeruleus controls bulbo-spinal seizure activity.
    • Neostriatal dopamine depletion is a reliable indicator of seizure resistance, though its direct protective role requires further investigation.