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 [3H]γ-aminobutyric acid (GABA) and [3H]glutamate uptakes were carried out in slices of cerebral cortex and hippocampus. [3H]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 [3H]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 [3H]GABA uptake, suggesting that its anticonvulsant action is related to an increase in inhibitory tonus.
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The financial support by UFSM and FAPERGS/CNPq (PRONEX) research Grant No. 10/0005-1 is gratefully acknowledged.
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Wilhelm, E.A., Gai, B.M., Souza, A.C.G. et al. Involvement of GABAergic and glutamatergic systems in the anticonvulsant activity of 3-alkynyl selenophene in 21 day-old rats. Mol Cell Biochem 365, 175–180 (2012). https://doi.org/10.1007/s11010-012-1257-3
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DOI: https://doi.org/10.1007/s11010-012-1257-3