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Lindane Administration to the Rat Induces Modifications in the Regional Cerebral Binding of [ 3 H]Muscimol, [ 3 H]‐Flunitrazepam, and t‐[ 35 S]Butylbicyclophosphorothionate: An Autoradiographic Study
Author(s) -
Solà Carme,
Martínez Emili,
Camón Lluïsa,
Pazos Angel,
RodríguezFarré Eduard
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb13409.x
Subject(s) - lindane , flunitrazepam , chemistry , allosteric regulation , binding site , pharmacology , ligand (biochemistry) , muscimol , gabaa receptor , mechanism of action , receptor , stereochemistry , biochemistry , biology , pesticide , in vitro , agronomy
Abstract: The effect of lindane administration on the specific binding of ligands to different sites on the GABA A receptor‐ionophore complex was studied in the rat brain by receptor mapping autoradiography. [ 3 H]Muscimol (Mus), [ 3 H]flunitrazepam (Flu), and t ‐[ 35 S]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 [ 35 S]TBPS binding, which was present shortly after dosing. In addition, [ 3 H]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 [ 3 H]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 [ 3 H]‐Mus binding was detected shortly after lindane‐induced convulsions. The observed decrease in [ 35 S]TBPS binding is in agreement with the postulated action of lindane at the picrotoxinin binding site of the GABA A receptor chloride channel. The effects observed on the binding of [ 3 H]Flu and [ 3 H]Mus may be secondary to the action of lindane as an allosteric antagonist of the GABA A receptor.