2,3-Butanedione monoxime protects mice against the convulsant effect of picrotoxin by facilitating GABA-activated currents

Tracy Brightman, Jiang Hong Ye, Elizabeth Ortiz-Jimenez, Edward J. Flynn, Wen Hsien Wu, Joseph J. McArdle

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (IGABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on concentrations (100 μM-40 mM) decreased and lower concentrations (0.01 μM-0.001 μM) potentiatedIGABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect onIGABA. Finally, when 0.001 μM BDM, 10-30 μM PTX and GABA were co-applied the inhibitory effect of the toxin onIGABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA.

Original languageEnglish (US)
Pages (from-to)110-116
Number of pages7
JournalBrain research
Volume678
Issue number1-2
DOIs
StatePublished - Apr 24 1995

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Keywords

  • 2,3-Butanedione
  • 2,3-Butanedione monoxime
  • Anticonvulsant
  • Convulsion
  • Picrotoxin
  • Whole cell current in response to GABA
  • γ-Aminobutyric acid

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