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

doi:10.1016/0006-8993(89)90499-X

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

Washington University School of Medicine

Research output: Contribution to journal › Article › peer-review

27 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 language	English
Pages (from-to)	169-174
Number of pages	6
Journal	Brain Research
Volume	481
Issue number	1
DOIs	https://doi.org/10.1016/0006-8993(89)90499-X
State	Published - Feb 27 1989

Keywords

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

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title = "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",

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.",

keywords = "Barbiturate, Chloride ion channel, Picrotoxin, Picrotoxinin, Seizure-sensitive mice, Synaptoneurosome, γ-Aminobutyric acid receptor",

author = "Schwartz, {Rochelle D.} and Seale, {Thomas W.} and Phil Skolnick and Paul, {Steven M.}",

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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. / Schwartz, Rochelle D.; Seale, Thomas W.; Skolnick, Phil et al.
In: Brain Research, Vol. 481, No. 1, 27.02.1989, p. 169-174.

Research output: Contribution to journal › Article › peer-review

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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

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