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.

Article date: 1989/2/27

PubMed ID: 2539878

Journal name: Brain research (ISSN: 0006-8993)


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 [35S]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.

This document is available from: http://directlinks.cc/files/muscimol/2539878.pdf

Author List: Schwartz R D, Seale T W, Skolnick P, Paul S M

Publication Types: Comparative Study; Journal Article

Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Chlorides; Receptors, GABA-A; Picrotoxin; Muscimol; tert-butylbicyclophosphorothionate; Pentobarbital;

Mesh terms: Animals; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Chlorides/physiology; Dose-Response Relationship, Drug; Frontal Lobe/physiopathology; Male; Mice; Mice, Inbred BALB C/physiology; Mice, Inbred DBA/physiology; Muscimol/metabolism; Pentobarbital/pharmacology; Picrotoxin; Receptors, GABA-A/drug effects; Seizures/chemically induced; Species Specificity; Synaptosomes/physiology;

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