Dose-response analysis of phenytoin on electrically induced seizures and spontaneous activity of cerebellar Purkinje cells in the frog

Steven Johnson, W. K. Riker

Research output: Contribution to journalArticle

Abstract

The hypothesis that phenytoin exerts its anticonvulsant effect by increasing the spontaneous firing rate of cerebellar Purkinje cells was tested in frogs (Rana pipiens). Time-dose-effect relationships were first established for the anticonvulsant effect of phenytoin in intact frogs. Maximal seizures were induced by corneal electroshock (MES), and phenytoin was injected into the ventral lymph sac. At the time of peak effect (3 h), 20-40 mg/kg phenytoin protected 60-80% of frogs against tonic hindlimb extension (THE). With this functional data base, experiments were then undertaken to test the effect of phenytoin on Purkinje cell firing rates. Phenytoin was injected into the ventral lymph sac 30-45 min prior to anesthesia with tricaine. The cranium was opened, the dura mater overlying the cerebellum was removed, and the frog was then curarized. Single-unit extracellular recordings from Purkinje cells were made with NaCl-filled glass micropipettes 2-6 h after phenytoin injection, the expected time of maximum anticonvulsant effect. Effective anticonvulsant doses (20-40 mg/kg) of phenytoin produced no alteration in the spontaneous firing rates of cerebellar Purkinje cells compared to the rates in solvent-injected controls. Consequently, the hypothesis that the anticonvulsant effect of phenytoin is mediated by an action on Purkinje cell firing rates is not supported by the results of this study.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalEpilepsia
Volume23
Issue number2
StatePublished - 1982

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Purkinje Cells
Phenytoin
Anura
Seizures
Anticonvulsants
Lymph
Rana pipiens
Dura Mater
Electroshock
Hindlimb
Skull
Cerebellum
Glass
Anesthesia
Databases
Injections

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Dose-response analysis of phenytoin on electrically induced seizures and spontaneous activity of cerebellar Purkinje cells in the frog. / Johnson, Steven; Riker, W. K.

In: Epilepsia, Vol. 23, No. 2, 1982, p. 123-131.

Research output: Contribution to journalArticle

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