Chronic phenytoin treatment decreases GABAA but not beta-adrenoceptors in the cerebellum of young rats.
The effects of chronic treatment with phenytoin (50 mg/kg p.o. daily, for the first 30 days after birth) on GABAA and beta-adrenoceptors in the rat cerebellum were investigated by using in vitro quantitative autoradiography and binding assays with membranes. A significant decrease in [3H]muscimol binding to GABAA sites and, to a lesser extent, [3H]flunitrazepam binding to benzodiazepine sites was observed in the granular and molecular layers of the cerebellar cortex at the end of the treatment. Scatchard analyses demonstrated that these effects were associated with a decreased Bmax for the respective binding sites in cerebellar membranes the (Kd was not changed). In contrast, [125I]cyanopindolol binding remained unaffected. These data provide further support for the involvement of GABAergic synapses in the anticonvulsant action of phenytoin.
Ruiz
G
G
Département de Cytologie, Université Pierre et Marie Curie, Paris, France.
Hamon
M
M
Vergé
D
D
D000319:Adrenergic beta-Antagonists; D000818:Animals; D001345:Autoradiography; D002531:Cerebellum / Q000648:ultrastructure*; D005260:Female; D005445:Flunitrazepam; D007700:Kinetics; D009118:Muscimol; D010672:Phenytoin / Q000494:pharmacology*; D010869:Pindolol / Q000031:analogs & derivatives; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D014316:Tritium; D009118:Muscimol; C047975:cyanopindolol; D010672:Phenytoin; D005445:Flunitrazepam; D010869:Pindolol