Lindane administration to the rat induces modifications in the regional cerebral binding of [3H]Muscimol, [3H]-flunitrazepam, and t-[35S]butylbicyclophosphorothionate: an autoradiographic study.
The effect of lindane administration on the specific binding of ligands to different sites on the GABAA receptor-ionophore complex was studied in the rat brain by receptor mapping autoradiography. [3H]Muscimol (Mus), [3H]flunitrazepam (Flu), and t-[35S]butylbicyclophosphorothionate (TBPS) were used as specific ligands of GABA, benzodiazepine, and picrotoxinin binding sites, respectively. Rats received a single oral dose of 30 mg/kg lindane and they were classified into two groups according to the absence or presence of convulsions. Vehicle-treated groups acted as controls. The effect of the xenobiotic on ligand binding was measured in different brain areas and nuclei 12 min or 5 h after its administration. Lindane induced a generalized decrease in [35S]TBPS binding, which was present shortly after dosing. In addition, [3H]Flu binding was increased in lindane-treated animals, this modification also appearing shortly after administration but diminishing during the studied time. Finally, lindane induced a decrease in [3H]Mus binding, which became more evident over time. These modifications were observed both in the presence and in the absence of convulsions. However, an increase in [3H]-Mus binding was detected shortly after lindane-induced convulsions. The observed decrease in [35S]TBPS binding is in agreement with the postulated action of lindane at the picrotoxinin binding site of the GABAA receptor chloride channel. The effects observed on the binding of [3H]Flu and [3H]Mus may be secondary to the action of lindane as an allosteric antagonist of the GABAA receptor.
Solà
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C
Department of Pharmacology and Toxicology, CSIC, Barcelona, Spain.
Martínez
E
E
Camón
L
L
Pazos
A
A
Rodríguez-Farré
E
E
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism*; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013462:Sulfur Radioisotopes; D014018:Tissue Distribution; D014316:Tritium
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants; D013462:Sulfur Radioisotopes; D014316:Tritium; D009118:Muscimol; D001556:Hexachlorocyclohexane; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate