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Decreased Benzodiazepine Receptor Density in Rat Cerebellum Following Neurotoxic Doses of Phenytoin
Author(s) -
Mimaki Takashi,
Deshmukh Pushpa P.,
Yamamura Henry I.
Publication year - 1980
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.1471-4159.1980.tb09029.x
Subject(s) - phenytoin , cerebellum , flunitrazepam , benzodiazepine , endocrinology , medicine , chemistry , gabaa receptor , pharmacology , receptor , biology , epilepsy , neuroscience
The effect of acute and chronic administration of phenytoin on [ 3 H]‐flunitrazepam binding was examined in the rat cerebellum. There was no significant effect of phenytoin on [ 3 H]flunitrazepam binding in the rat cerebellum 1 and 6 h after a single i.p. injection of 200 mg/kg of phenytoin. However, after 14 days and 28 days of chronic phenytoin administration, significant de‐creases in [ 3 H]flunitrazepam receptor density were observed, with no changes in apparent affinity constants in the rat cerebellum. This effect of phenytoin was dose‐dependent, as lower doses of phenytoin (100 mg/kg/day) for 14 or 28 days produced no alterations in [ 3 H]flunitrazepam binding in the rat cerebellum. Light‐microscopic examination of the rat cerebellum treated with 200 mg/kg/day of phenytoin for 14 days showed degeneration of the Purkinje cells, with edematous Bergmann astrocytes. These data provide evidence for the neuronal localization of benzodiazepine receptors on cerebellar Purkinje cells.