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

Abstract

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.

• Authors: Giovambattista De Sarro, Guido Ferreri Ibbadu, Rosario Marra, Domenicantonio Rotiroti, Antonella Loiacono, Eugenio Donato Di Paola, Emilio Russo
• Journal: Neuroscience research (Neurosci Res) Vol. 50 Issue 1 Pg. 37-44 (Sep 2004) ISSN: 0168-0102 [Print] Ireland
• PMID: 15288497 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Convulsants
• Dystrophin
• Excitatory Amino Acid Antagonists
• GABA Antagonists
• Potassium Channel Blockers
• Pentylenetetrazole

Topics

• Acute Disease
• Animals
• Chronic Disease
• Convulsants (pharmacology)
• Disease Models, Animal
• Dystrophin (deficiency, genetics)
• Epilepsy (chemically induced, genetics, physiopathology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Female
• GABA Antagonists (pharmacology)
• Genetic Predisposition to Disease (genetics)
• Kindling, Neurologic (drug effects, genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Inbred mdx
• Pentylenetetrazole (pharmacology)
• Potassium Channel Blockers (pharmacology)
• Reaction Time (drug effects, genetics)
• Species Specificity
• Stimulation, Chemical