Effect of various serotoninergically induced manipulations on audiogenic seizures in magnesium-deficient mice.
The aim of our study was to analyse the possible implication of the serotoninergic system in the pathophysiology and the lethality of audiogenic seizures induced by magnesium deficiency, either by decreasing cerebral serotonin (5-HT) levels (p-chlorophenylalanine) or by increasing 5-HT levels in the brain (5-hydroxytryptophan, L-tryptophan, nialamide, fluoxetine). In magnesium-deficient mice, the percentages of audiogenic seizures and of fatal seizures were dependent on the time lapse between the p-chlorophenylalanine (PCPA) injection and the audiogenic test. The percentage was at least 24 h after the injection: in OF1 and C57BL/6 strains, PCPA fully protected the mice from seizure occurrence, whereas it only partially protected the animals of the other strains. 5-Hydroxytryptophan caused a decrease in the audiogenic seizures in magnesium-deficient OF1 mice as well as in control DBA/2 mice. In contrast L-tryptophan did not reduce the number of wild courses or of clonic and tonic seizures in either the magnesium-deficient OF1 strain or control DBA/2 mice. Nialamide and fluoxetine were only effective in decreasing the numbers of clonic and tonic convulsions of the audiogenic seizure without affecting the wild courses. The combination of nialamide and tryptophan caused a cessation of the audiogenic seizure phases in both magnesium-deficient OF1 and control DBA/2 mice. In contrast, the fluoxetine-tryptophan combination did not have the same effect on magnesium-deficient and non-magnesium-deficient mice. This work showed that the serotoninergic system plays a secondary role in the pathophysiology of audiogenic seizures in magnesium-deficient mice rather than in that of genetically audiosusceptible mice.
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Laboratoire de Biologie Animale Appliquée, Faculté de Pharmacie, Châtenay Malabry, France.
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Herrenknecht
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Dewulf
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Binet
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Durlach
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D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D010134:Fenclonine / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D008275:Magnesium Deficiency / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009526:Nialamide / Q000494:pharmacology; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism*; D013045:Species Specificity; D014364:Tryptophan / Q000494:pharmacology*
D005473:Fluoxetine; D012701:Serotonin; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D010134:Fenclonine; D009526:Nialamide