PURPOSE: Antagonists of group I metabotropic glutamate receptors (mGluRs) are known to exhibit anticonvulsant action without serious side effects. Recently we found anticonvulsant effects of specific antagonists of mGluR subtypes 1 and 5 (AIDA and MTEP) against pentetrazol-induced convulsions in developing rats. In order to determine if the effects of these two antagonists are not exclusively restricted to pentetrazol-induced seizures, we studied their action in a novel seizure model involving immature rats. METHODS: Epileptic afterdischarges were elicited by low-frequency stimulation of sensorimotor cortical region in 12-, 18-, and 25-day-old rats with implanted electrodes. Drugs were administered intraperitoneally after the first afterdischarge: AIDA in doses from 5 to 40 mg/kg; MTEP in doses from 2.5 to 40 mg/kg. The stimulation was then repeated five more times with the same current intensity. Electrocorticographic and motor phenomena were recorded and evaluated. RESULTS: AIDA did not significantly influence movements during stimulation, afterdischarges as well as clonic seizures accompanying afterdischarges. In contrast, MTEP was able to significantly shorten afterdischarges without changes in the two motor phenomena. The effect of MTEP was best expressed in 12-day-old rats; in 25-day-old rats the trials exhibited only a transient shortening of afterdischarges after high doses of MTEP. DISCUSSION: In contrast to similar action against pentetrazol-induced seizures, AIDA and MTEP substantially differ in their action on cortical epileptic afterdischarges. The anticonvulsant action of MTEP in the present model diminishes with age.
- MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- antikonvulziva farmakologie MeSH
- elektroencefalografie statistika a číselné údaje MeSH
- epilepsie chemicky indukované patofyziologie prevence a kontrola MeSH
- financování organizované MeSH
- konvulziva farmakologie MeSH
- krysa rodu rattus MeSH
- mozková kůra patofyziologie účinky léků MeSH
- novorozená zvířata MeSH
- pentylentetrazol farmakologie MeSH
- pohybová aktivita fyziologie účinky léků MeSH
- potkani Wistar MeSH
- pyridiny farmakologie MeSH
- receptory metabotropního glutamátu antagonisté a inhibitory MeSH
- receptory N-methyl-D-aspartátu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Antagonists of type I of metabotropic glutamate receptors exhibit anticonvulsant action in adult as well as immature rodents. To know the anticonvulsant profile of a specific mGluR5 antagonist MPEP in developing rats, two models of epileptic seizures were used. MPEP (10, 20 or 40 mg/kg i.p.) suppressed in a dose-dependent manner epileptic afterdischarges induced by electrical stimulation of sensorimotor cortical area in three age groups (12, 18 and 25 days old). The anticonvulsant action was more expressed in the youngest group than in older animals so that in 25-day-old rats an additional dose of 80 mg/kg was used. In contrast to this marked anticonvulsant action, MPEP at a dose of 40 mg/kg i.p. in 18-day-old rat pups and at doses of 40 and 80 mg/kg in 25-day-old rat pups did not affect episodes of spike-and-wave rhythm elicited by low doses of pentetrazol. Our results delineate the profile of the anticonvulsant action of MPEP and confirm the higher efficacy of this antagonist at early developmental stages in comparison with prepubertal animals.
- MeSH
- absentní epilepsie farmakoterapie chemicky indukované MeSH
- analýza rozptylu MeSH
- antikonvulziva terapeutické užití MeSH
- elektrická stimulace škodlivé účinky MeSH
- elektroencefalografie metody MeSH
- epilepsie etiologie farmakoterapie MeSH
- financování organizované MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra patofyziologie účinky léků účinky záření MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- pyridiny terapeutické užití MeSH
- reakční čas fyziologie účinky léků účinky záření MeSH
- receptory metabotropního glutamátu antagonisté a inhibitory MeSH
- věkové faktory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
