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Metabotropic glutamate receptors as a target for anticonvulsant and anxiolytic action in immature rats
P. Mares, A. Mikulecká, K. Tichá, D. Lojková-Janecková, H. Kubová,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
NLK
Free Medical Journals
od 1997 do Před 1 rokem
Wiley Online Library (archiv)
od 1997-01-01 do 2012-12-31
Wiley Free Content
od 1997 do Před 4 lety
- MeSH
- antikonvulziva farmakologie MeSH
- anxiolytika farmakologie MeSH
- elektrická stimulace MeSH
- epilepsie chemicky indukované farmakoterapie MeSH
- indany farmakologie terapeutické užití MeSH
- krysa rodu rattus MeSH
- psychomotorický výkon účinky léků MeSH
- pyridiny farmakologie terapeutické užití MeSH
- receptory metabotropního glutamátu antagonisté a inhibitory MeSH
- thiazoly farmakologie terapeutické užití MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Antagonists of group I of metabotropic glutamate receptors (mGluRs) exhibit anticonvulsant as well as anxiolytic action in adult rodents. Therefore, we started to study these effects in developing rats. Motor seizures induced by pentylenetetrazol (PTZ) and cortical epileptic afterdischarges (CxADs) elicited by electrical stimulation were used in immature rats. High doses of antagonists were needed to demonstrate anticonvulsant effects. Antagonist of mGluR1 AIDA [(R,S)-1-aminoindan-1,5-dicarboxylic acid] suppressed the tonic phase of PTZ-induced generalized tonic-clonic seizures in 7-, 12-, and 18-day-old rats, but not in 25-day-old rats. No significant effect of AIDA against CxADs was found. Antagonists of mGluR5-MPEP [2-methyl-6-(phenylethynyl)-pyridine] and MTEP [3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine] exhibited the same effect against PTZ-induced seizures as AIDA. In addition, they exhibited an anticonvulsant action against CxADs in 12- and 18-day-old rats. No drug compromised motor performance. Anxiolytic action of all three antagonists was demonstrated in light/dark box or in elevated plus maze tests. Homing reaction was used as an age-appropriate test of learning. AIDA did not affect homing, whereas the highest dose of MPEP compromised this behavior in 12- and partially in 18-day-old rats. The three antagonists possess age-dependent anticonvulsant as well as anxiolytic action, with minimal negative side effects.
Citace poskytuje Crossref.org
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- $a Mares, Pavel $u Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences, Prague, Czech Republic. maresp@epilepsy.biomed.cas.cz
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- $a Antagonists of group I of metabotropic glutamate receptors (mGluRs) exhibit anticonvulsant as well as anxiolytic action in adult rodents. Therefore, we started to study these effects in developing rats. Motor seizures induced by pentylenetetrazol (PTZ) and cortical epileptic afterdischarges (CxADs) elicited by electrical stimulation were used in immature rats. High doses of antagonists were needed to demonstrate anticonvulsant effects. Antagonist of mGluR1 AIDA [(R,S)-1-aminoindan-1,5-dicarboxylic acid] suppressed the tonic phase of PTZ-induced generalized tonic-clonic seizures in 7-, 12-, and 18-day-old rats, but not in 25-day-old rats. No significant effect of AIDA against CxADs was found. Antagonists of mGluR5-MPEP [2-methyl-6-(phenylethynyl)-pyridine] and MTEP [3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine] exhibited the same effect against PTZ-induced seizures as AIDA. In addition, they exhibited an anticonvulsant action against CxADs in 12- and 18-day-old rats. No drug compromised motor performance. Anxiolytic action of all three antagonists was demonstrated in light/dark box or in elevated plus maze tests. Homing reaction was used as an age-appropriate test of learning. AIDA did not affect homing, whereas the highest dose of MPEP compromised this behavior in 12- and partially in 18-day-old rats. The three antagonists possess age-dependent anticonvulsant as well as anxiolytic action, with minimal negative side effects.
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