Abstract | PURPOSE: METHODS: Random crosses involving eight inbred mice strains were used to generate the starting population in which the first MSO challenge (75 mg/kg, i.p.) was performed. Two groups of 16 breeding pairs were established by mating mice having the shortest (MSO-Fast) and the longest (MSO-Slow) convulsion latencies. Mating and selection by latency to MSO (75 mg/kg, i.p.) was carried out over six generations. RESULTS: MSO-Fast mice presented a significantly shorter MSO latency, and were more susceptible to MSO than MSO-Slow ones were. Electroencephalography (EEG) alterations were observed during the preconvulsive period when MSO-Fast mice were submitted to 75 mg/kg of MSO, and MSO-Slow ones to 200 mg/kg. Using another convulsant, kainic acid, the latency to convulse of MSO-Fast mice was significantly shorter than that of the MSO-Slow ones, whereas no difference was observed in response to pentylenetetrazole (PTZ). MSO-dependent convulsions were completely antagonized by MK-801, and partially by valproic acid, suggesting a preferential involvement of glutamatergic pathways. DISCUSSION: The model that we have developed for MSO "sensitive" and "resistant" mice could allow for a better understanding of MSO mechanisms of epileptogenesis, and it may also constitute a useful approach for therapeutic actions of drugs.
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Authors | Jean-François Cloix, Zahir Tahi, Benoît Martin, Tobias Hévor |
Journal | Epilepsia
(Epilepsia)
Vol. 51
Issue 1
Pg. 118-28
(Jan 2010)
ISSN: 1528-1167 [Electronic] United States |
PMID | 20015245
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Convulsants
- Methionine Sulfoximine
- Dizocilpine Maleate
- Kainic Acid
- Pentylenetetrazole
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Topics |
- Animals
- Cerebral Cortex
(drug effects, physiology)
- Convulsants
(pharmacology)
- Crosses, Genetic
- Disease Models, Animal
- Dizocilpine Maleate
(pharmacology)
- Dose-Response Relationship, Drug
- Electrodes, Implanted
- Electroencephalography
(statistics & numerical data)
- Female
- Kainic Acid
(pharmacology)
- Male
- Methionine Sulfoximine
(administration & dosage, pharmacology)
- Mice
- Mice, Inbred C57BL
- Mice, Inbred CBA
- Pentylenetetrazole
(pharmacology)
- Reaction Time
(drug effects, genetics)
- Seizures
(chemically induced, genetics)
- Selection, Genetic
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