Diphenyl diselenide-induced seizures in rat pups: possible interaction with GABAergic system.
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.
Prigol
Marina
M
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Brazil.
Wilhelm
Ethel A
EA
Nogueira
Cristina W
CW
Zeni
Gilson
G
D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001555:Benzene Derivatives; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018757:GABA Modulators / Q000494:pharmacology; D016566:Organoselenium Compounds; D010634:Phenobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000083:Acetanilides; D001555:Benzene Derivatives; D003975:Diazepam; D018757:GABA Modulators; D016566:Organoselenium Compounds; D010634:Phenobarbital; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C061132:diphenyldiselenide; C002605:DABA