title: Anticonvulsant and behavioral effects of muscimol in immature rats.
abstract: Potentiation of GABAergic inhibition is a mechanism of action of many antiepileptic drugs. The potential use of an agonist of GABAA receptors, muscimol, as an antiepileptic drug was studied in immature rats by assessing anticonvulsant activity and side effects on motor activities. Anticonvulsant action was tested in two models of seizures (pentetrazol-induced convulsions and cortical epileptic afterdischarges). Off target effect on motor performance was assessed in a battery of tests and in the open field in three age groups (12-, 18- and 25-day-old rats). Muscimol was administered in doses from 0.1 to 1mg/kg i.p. Only the 1 mg/kg dose exhibited marked anticonvulsant effect against pentetrazol-induced convulsions in 12- and 18-day-old rats, proconvulsant effect was observed in the second model in 18- and 25-day-old rats as prolongation of afterdischarges. Even the 0.5 mg/kg dose suppressed spontaneous locomotion and heavily compromised motor performance. The effect on motor activity was marked in the youngest group and decreased with age. Due to the low anticonvulsant potency and serious side effects, systemic administration of a competitive agonist of GABAA receptors in immature animals is not a promising strategy for new anticonvulsants.
authors.affiliation: Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences, Czech Republic. Electronic address: maresp@biomed.cas.cz.
authors.forename: Pavel
authors.initials: P
authors.lastname: Mareš
authors.affiliation: Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences, Czech Republic; Charles University, 2nd Medical Faculty, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Tichá
authors.affiliation: Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Mikulecká
mesh_terms: D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology*; D009483:Neuropsychological Tests; D010433:Pentylenetetrazole; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D000927:Anticonvulsants; D058785:GABA-A Receptor Agonists; D009118:Muscimol; D010433:Pentylenetetrazole
keywords: Cortical afterdischarges; Motor activities; Muscimol; Ontogeny; Pentetrazol-induced seizures; Rat