Anticonvulsant action of GABA_B receptor positive modulator CGP7930 in immature rats

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• 作者：Pavel Mare&scaron ; ; ^{maresp@biomed.cas.cz}
• 关键词：Pentetrazol ; Motor seizures ; GABAB receptors ; Development ; Rat
• 刊名：Epilepsy Research
• 出版年：2012
• 期刊代码：87_09201211
• 类别：med
• 出版时间：June, 2012
• 卷：100
• 期：1-2
• 页码：49-54
• 文件大小：1010 K

摘要

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Summary

GABA_B receptors mediate inhibition at early stages of development but mixed anti-and proconvulsant action of their agonists affecting all receptors was found in immature rats. Positive allosteric modulators of GABA_B receptors potentiate only already active GABA_B receptors and therefore more specific action is expected. Possible anticonvulsant action of CGP7930 was studied in a model of pentetrazol-induced seizures previously used for studies with agonists baclofen and SKF97541.

Pentetrazol (100 mg/kg) was administered subcutaneously in male rats 7, 12, 18, 25 and 90 days old pretreated with CGP7930 in doses 1-40 mg/kg i.p.

High doses of CGP7930 suppressed generalized tonic-clonic seizures in all five age groups. Animals 18 and less days old exhibited a specific suppression of the tonic phase after lower doses of CGP7930. Twelve-day-old rats were the most sensitive to anticonvulsant effect of CGP7930 (even the 2-mg/kg dose suppressed the tonic phase whereas 20-mg/kg dose was active in other age groups). Minimal clonic seizures (mS) were moderately potentiated by low doses of CGP7930 in 18-day-old but suppressed by the highest dose in 25-day-old rats. The 60-mg/kg dose of PTZ induced only mS in 4 out of 9 25-day-old rats; the 40-mg/kg dose of CGP7930 combined with this lower dose of PTZ resulted in the only proconvulsant effect - generalized tonic-clonic seizures appeared in two rats.

Results from 12-day-old rats suggest a possibility to find an age-specific anticonvulsant among positive allosteric modulators of GABA_B receptors.