Differential seizure sensitivities to picrotoxinin in two inbred strains of mice (DBA/2J and BALB/c ByJ): parallel changes in GABA receptor-mediated chloride flux and receptor binding

Rochelle D. Schwartz, Thomas W. Seale, Phil Skolnick, Steven M. Paul

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Two strains of mice were shown to possess a differential sensitivity to picrotoxinin-induced convulsions; picrotoxinin elicited both tonic and clonic seizures at lower doses in the DBA/2J (DBA) strain compared to the BALB/c ByJ (BALB) strain. Less protection of picrotoxinin-induced tonic seizures was afforded by pentobarbital in the DBA strain. Biochemical studies revealed that picrotoxin inhibited 36Cl- efflux from forebrain synaptoneurosomes only in the DBA strain. In addition, picrotoxin inhibited pentobarbital-induced 36Cl- efflux to a greater extent in the DBA strain. No differences were observed in the binding of [3H]muscimol or [3H] t-butylbicyclophosphorothionate (TBPS) to forebrain homogenates, while pentobarbital was a less potent inhibitor of [35S]TBPS binding in the DBA strain. These findings suggest a genetic basis for the behavioral differences in convulsant sensitivity as well as for the neurochemical differences in allosteric coupling between convulsant and depressant/anticonvulsant sites associated with the GABA receptor-gated Cl- channel.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalBrain Research
Volume481
Issue number1
DOIs
StatePublished - Feb 27 1989
Externally publishedYes

Keywords

  • Barbiturate
  • Chloride ion channel
  • Picrotoxin
  • Picrotoxinin
  • Seizure-sensitive mice
  • Synaptoneurosome
  • γ-Aminobutyric acid receptor

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