Selection of two lines of mice based on latency to onset of methionine sulfoximine seizures.
OBJECTIVE
In various animals methionine sulfoximine (MSO) induces tonic-clonic seizures resembling the most striking form of human epilepsies. The aim of the present study was to select two lines of mice based upon differences in their latency to MSO-dependent seizures, in order to characterize them.


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.


CONCLUSIONS
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.
Cloix
Jean-François
JF
Laboratoire de Neurobiologie, Rue de Chartres, Université d'Orléans, BP 6759, 45067 Orléans Cedex 2, France. jean-francois.cloix@univ-orleans.fr
Tahi
Zahir
Z
Martin
Benoît
B
Hévor
Tobias
T
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003292:Convulsants / Q000494:pharmacology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008717:Methionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010433:Pentylenetetrazole / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics; D012641:Selection, Genetic
D003292:Convulsants; D008717:Methionine Sulfoximine; D016291:Dizocilpine Maleate; D007608:Kainic Acid; D010433:Pentylenetetrazole