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Diphenyl diselenide-induced seizures in rat pups: possible interaction with GABAergic system.

AbstractOBJECTIVES:
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.
DISCUSSION:
Our findings demonstrated that seizures induced by (PhSe)₂ are mediated, at least in part, by an interaction with GABAergic system.
AuthorsMarina Prigol, Ethel A Wilhelm, Cristina W Nogueira, Gilson Zeni
JournalNeurological research (Neurol Res) Vol. 32 Issue 9 Pg. 1002-8 (Nov 2010) ISSN: 1743-1328 [Electronic] England
PMID20433775 (Publication Type: Journal Article)
Chemical References
  • Acetanilides
  • Benzene Derivatives
  • GABA Modulators
  • Organoselenium Compounds
  • Picrotoxin
  • diphenyldiselenide
  • DABA
  • gamma-Aminobutyric Acid
  • Diazepam
  • Phenobarbital
Topics
  • Acetanilides (pharmacology)
  • Animals
  • Animals, Newborn
  • Benzene Derivatives
  • Diazepam (pharmacology)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • GABA Modulators (pharmacology)
  • Organoselenium Compounds
  • Phenobarbital (pharmacology)
  • Picrotoxin (pharmacology)
  • Rats
  • Seizures (chemically induced, metabolism)
  • gamma-Aminobutyric Acid (metabolism)

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