[Effects of ionotropic glutamate receptor channel blockers on the development of audiogenic seizures in Krushinski-Molodkina rats]
| Autor: | N Ia, Lukomskaia, S I, Vataev, E P, Zhabko, L G, Magazanik |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cyclohexylamines Adamantane Diamines Motor Activity Injections Intramuscular Receptors N-Methyl-D-Aspartate Drug Administration Schedule Epilepsy Reflex Rats Quaternary Ammonium Compounds Acoustic Stimulation Receptors Kainic Acid Memantine Seizures Animals Receptors AMPA Excitatory Amino Acid Antagonists |
| Zdroj: | Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova. 98(4) |
| ISSN: | 0869-8139 |
| Popis: | The action of noncompetitive blockers of glutamate receptors has been investigated on Krushinski-Molodkina rats genetically-prone to audiogenic seizures. The selective blockers of NMDA receptor channels, memantine and IEM-1921, and their dicationic homologues, IEM-1925 and IEM-1754, capable of blocking in varying degrees both NMDA and Ca-permeable AMPA receptor channels, were studied. The drugs were injected intramuscularly to rats with the different time intervals (30 min, 1, 2 or 3 hours) before sound signal. The effects of the drugs on latent period of initial locomotor activity provoked by audio stimulation (8 kHz sine-wave tone, 90 dB volume), the appearance of clonic convulsions of different intensities, and, finally, tonic convulsions with limb and tail extension were evaluated. Within 30 min after injection IEM-1921 at a dose of 5 mg/kg, 33% of rats manifested a complete absence of convulsive reactions to sound, and in 59% of rats audiogenic seizures occured only in the form of motor excitation without a generalized clonic-tonic convulsions. Memantine at a dose of 5 mg/kg did not cause a complete blockade of seizures, but after 1 h of injection in 50% of the rats and after 2 h in 70% of rats a weakening of the audiogenic seizures to the level of motor excitation only was observed. After 3 hrs after administration of blockers its anticonvulsive action weakened significantly (p0.01). Dicationic blockers that block both NMDA and AMPA/kainate receptors, IEM-1925 (in doses of 0.001-20.0 mg/kg) and IEM-1754 (0.025-50.0 mg/kg), did not affect audiogenic clonic-tonic convulsive reactions. The involvement of activation of NMDA and calcium permeable AMPA/kainate receptors in the pathogenesis of audiogenic seizures is discussed. |
| Databáze: | OpenAIRE |
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