title: Involvement of GABAergic and glutamatergic systems in the anticonvulsant activity of 3-alkynyl selenophene in 21 day-old rats.
abstract: In this study, we investigated the role of GABAergic and glutamatergic systems in the anticonvulsant action of 3-alkynyl selenophene (3-ASP) in a pilocarpine (PC) model of seizures. To this purpose, 21 day-old rats were administered with an anticonvulsant dose of 3-ASP (50 mg/kg, per oral, p.o.), and [(3)H]γ-aminobutyric acid (GABA) and [(3)H]glutamate uptakes were carried out in slices of cerebral cortex and hippocampus. [(3)H]GABA uptake was decreased in cerebral cortex (64%) and hippocampus (58%) slices of 21 day-old rats treated with 3-ASP. In contrast, no alteration was observed in [(3)H]glutamate uptake in cerebral cortex and hippocampus slices of 21 day-old rats that received 3-ASP. Considering the drugs that increase synaptic GABA levels, by inhibiting its uptake or catabolism, are effective anticonvulsants, we further investigated the possible interaction between sub-effective doses of 3-ASP and GABA uptake or GABA transaminase (GABA-T) inhibitors in PC-induced seizures in 21 day-old rats. For this end, sub-effective doses of 3-ASP (10 mg/kg, p.o.) and DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake--2 mg/kg, intraperitoneally; i.p.) or aminooxyacetic acid hemihydrochloride (AOAA; a GABA-T inhibitor--10 mg/kg, i.p.) were co-administrated to 21 day-old rats before PC (400 mg/kg; i.p.) treatment, and the appearance of seizures was recorded. Results demonstrated that treatment with AOAA and 3-ASP or DABA and 3-ASP significantly abolished the number of convulsing animals induced by PC. The present study indicates that 3-ASP reduced [(3)H]GABA uptake, suggesting that its anticonvulsant action is related to an increase in inhibitory tonus.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Ethel Antunes
authors.initials: EA
authors.lastname: Wilhelm
authors.forename: Bibiana Mozzaquatro
authors.initials: BM
authors.lastname: Gai
authors.forename: Ana Cristina Guerra
authors.initials: AC
authors.lastname: Souza
authors.forename: Cristiani Folharini
authors.initials: CF
authors.lastname: Bortolatto
authors.forename: Juliano Alex
authors.initials: JA
authors.lastname: Roehrs
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C574375:1-(2,5-diphenylselenophen-3-yl)-3-methylpent-1-yn-3-ol; D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D016566:Organoselenium Compounds; D010862:Pilocarpine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid