Diphenyl diselenide-induced seizures in rat pups: possible interaction with GABAergic system.
キーワード
概要
OBJECTIVE
The involvement of the GABAergic system in seizures induced by diphenyl diselenide (PhSe)₂ in rat pups was investigated.
METHODS
To this end, the effect of aminooxyacetic acid hemihydrochloride (AOAA, 20 mg/kg; by intraperitoneal route, i.p.), a GABA-T inhibitor; DL-2,4-diamino-n-butyric acid hydrochloride (DABA, 16 mg/kg; i.p.), an inhibitor of GABA uptake; and γ-aminobutyric acid (GABA, 10 and 40 mg/kg; i.p.), diazepam (3 mg/kg; i.p.) and phenobarbital (40 mg/kg; i.p.), GABAergic agonists as well as picrotoxin (1 mg/kg; i.p.), a GABAA receptor antagonist on (PhSe)₂ (50 and 500 mg/kg, by oral route, p.o.)-induced seizures, were studied. The [(3)H]GABA uptake levels by cortical and hippocampal slices in rat pups exposed to (PhSe)₂ were also carried out.
RESULTS
Pre-treatment with GABA (40 mg/kg), diazepam, phenobarbital, AOAA and DABA abolished the appearance of seizures induced by 50 mg/kg (PhSe)₂ in rat pups. Picrotoxin increased the percentage of convulsing rat pups from 42 to 100% and reduced significantly the onset for the first convulsive episode induced by (PhSe)₂ at the dose of 50 mg/kg. Diazepam and phenobarbital prolonged significantly the latency for the onset of the first convulsive episode caused by 500 mg/kg (PhSe)₂ in rat pups. [(3)H]GABA uptake levels were stimulated in cerebral cortical and hippocampal slices of convulsing rat pups administered with both doses of (PhSe)₂.
CONCLUSIONS
Our findings demonstrated that seizures induced by (PhSe)₂ are mediated, at least in part, by an interaction with GABAergic system.
