Seizure susceptibility to various convulsant stimuli in dystrophin-deficient mdx mice.

In the present study, the susceptibility of the mdx mouse, a dystrophin-deficient genetic model of Duchenne muscular dystrophy (DMD), to various convulsant stimuli has been evaluated and compared to three related mice strains (C57BL/6J, C57BL/10 and DBA/2 mice). Animals were treated with chemical convulsants impairing gamma-aminobutyric acid (GABA) neurotransmission [pentylenetetrazole, picrotoxin, bicuculline, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), methyl-beta-carboline-3-carboxylate (beta-CCM)], enhancing glutamatergic neurotransmission [N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainic acid (KA)] or a K(+) channel blocker (4-aminopyridine). Occurrence of clonic and/or tonic seizures was evaluated to observe possible differences in seizure susceptibility. In addition, all strains of mice were repeatedly treated with a subconvulsant dose of pentylenetetrazole (PTZ) for possible differences in kindling development. The mdx mice exhibited no difference in seizure susceptibility for all convulsant drugs with the exception of a significantly lower sensitivity to AMPA and KA than the other mice strains. This study demonstrates that mdx mice possess a decreased susceptibility to some convulsant stimuli. However, mdx mice showed an enhanced seizure severity and a shorter latency in the development of chemical kindling produced by administration of PTZ. The present data suggests that the dystrophin deficiency in mdx mice affects the pathophysiology and pharmacology of acute and chronic epileptic seizures in an opposite manner.