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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.
Abstract:
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg s.c. for 5 days) to mice resulted in complete abolishment of strychnine seizure and of the tonic phase of the maximal electroshock response. Bicuculline and picrotoxin convulsions were not significantly affected by MPTP treatment. The severity of the pentylenetetrazole seizures was mildly, but significantly affected in the protective way. MPTP depleted neostriatal dopamine and its metabolites, together with hippocampal norepinephrine. No nigral neuronal loss was detected histologically. Strychnine seizures and the tonic phase of the maximal electroshock response are thought to depend mostly on hindbrain (bulbo-spinal) structures. Thus, these experiments suggest that a caudally projecting system originates from the substantia nigra, pars compacta, and/or locus coeruleus, controlling seizures that involve bulbo-spinal centers. While neostriatal dopamine depletion offers a good index of seizure resistance, its role in the protection from seizures remains to be established.
Insights
MPTP administration abolished strychnine and maximal electroshock seizures in mice by affecting hindbrain structures. Dopamine depletion correlated with seizure resistance, suggesting a protective role.
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.
- 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.