Subchronic treatment with cyclosporin A decreases the binding properties of the GABAA receptor in ovariectomized rats.
In this study, we investigated the effect of cyclosporin A on the binding properties of the GABAA receptor in the hippocampus, known to be responsible for the induction of seizures, to clarify the mechanism of cyclosporin A-inhibited GABA neurotransmission in ovariectomized rats, as a climacterium model. The effects of single and subchronic treatments with cyclosporin A were examined on [3H]muscimol binding to hippocampal synaptosomal membranes in sham, ovariectomized, and estradiol/ovariectomized rats. A single treatment with cyclosporin A (40 mg/kg, i.p.) failed to change [3H]muscimol binding in the 3 groups, when compared with each corresponding vehicle-treated group. Subchronic treatment with cyclosporin A (40 mg/kg, i.p., once a day for 5 days) significantly decreased the amount of [3H]muscimol binding in ovariectomized rats. However, this inhibitory effect was not observed in sham or estradiol/ovariectomized rats. These results demonstrated that the binding activity of the GABAA receptor was decreased in ovariectomized rats after subchronic cyclosporin A treatment. This study supports the hypothesis that ovariectomy elevates the susceptibility to cyclosporin A-induced convulsions by accelerating the inhibitory actions of cyclosporin A on GABA neurotransmission in the hippocampus.
Tominaga
Koji
K
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan, 814-0180, Fukuoka, Japan.
Kai
Mamiko
M
Yamauchi
Atsushi
A
Dohgu
Shinya
S
Toda
Kayoko
K
Oishi
Ryozo
R
Kataoka
Yasufumi
Y
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D003864:Depression, Chemical; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009118:Muscimol / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*
D018755:GABA Agonists; D007166:Immunosuppressive Agents; D011963:Receptors, GABA-A; D009118:Muscimol; D004958:Estradiol; D016572:Cyclosporine