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Bicuculline Up‐Regulation of GABA A Receptors in Rat Brain
Author(s) -
Ito Yoshihisa,
Lim Dong Koo,
Hoskins Beth,
Ho Ing K.
Publication year - 1988
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.1471-4159.1988.tb04848.x
Subject(s) - bicuculline , muscimol , striatum , gabaa receptor , endocrinology , chemistry , medicine , cerebellum , frontal cortex , cortex (anatomy) , neuroscience , receptor , pharmacology , biology , biochemistry , dopamine
Effects of acute and subacute administration of Dicuculline on [ 3 H]muscimol, [ 3 H]flunitrazepam, and t‐ [ 35 S]butylbicyclophosphorothionate ([ 35 S]TBPS) binding to various brain regions were studied in Sprague‐Dawley rats. Acute administration of bicuculline affected neither the K D nor the B max of the three receptor sites. In rats treated sub‐acutely with bicuculline (2 mg/kg, i.p., daily for 10 days), [ 3 H]muscimol binding was increased in the frontal cortex, cerebellum, striatum, and substantia nigra. Scatchard analysis revealed that subacute treatment of rats with bicuculline resulted in a significantly lower K D of high‐affinity sites in the striatum and in a significantly lower K D of high‐ and low‐affinity sites in the frontal cortex. In the cerebellum, two binding sites were apparent in controls and acutely treated animals; however, only the high‐affinity site was defined in subacutely treated animals, with an increase in the B max value. Triton X‐100 treatment of frontal cortical membranes eliminated the difference in [ 3 H]muscimol binding between control and subacute bicuculline treatments. On the other hand, [ 3 H]muscimol binding was significantly increased in the cerebellum from bicuculline‐treated animals even after Triton X‐100 treatment. The apparent K i of bicuculline for the GABA A receptor was also decreased in the frontal cortex and the striatum following the treatment. However, subacute administration of bicuculline affected neither the K D nor the B max of [ 3 H]‐flunitrazepam and [ 35 S]TBPS binding in the frontal cortex and the cerebellum. These results suggest that GABA A receptors are up‐regulated after subacute administration of bicuculline, with no change in benzodiazepine and picro‐toxin binding sites.