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.