EXPERIMENTAL NEUROLOGY 66,524-532 (1979) Effect of Inhibitors of Protein Synthesis on the Development of Kindled Seizures in Rats VILIAM JONEC AND CLAUDE G. WASTERLAIN’ Epilepsy Research Laboratory, Sepulveda Veterans Administration Medical Center, and Department of Neurology and Brain Research Institute, University of California, School of Medicine, Los Angeles, California 90024 Received March 9, 1979; revision received July 11, 1979 The rate of development of kindled amygdaloid seizures in male Holzman rats was significantly reduced by injection of anisomycin (60 mg/kg, i.p.) or cycloheximide (1.5 or 2 mg/kg, s.c.), 30 min prior to each stimulation. This effect coincided with severe inhibition of brain protein synthesis, but not with anticonvulsant effects of either drug as judged by crossover of treatments or by seizure threshold testing. These results demonstrated that the retarding effect of inhibitors of protein synthesis on kindling is not due to an anticonvulsant action of these drugs. INTRODUCTION Kindling is characterized by the development, in response to sub- threshold stimulation of some brain structures, of an increase in response intensity culminating in generalized epileptic seizures and leading in some animals to spontaneous seizures (3, 4). The biochemical basis for this change in cerebral excitability is unknown. Transsynaptic enzyme induction, a well-established phenome- non in the peripheral nervous system and one possible mechanism for kindling, requires protein synthesis (9). Previous investigations of the possible effects of inhibitors of protein synthesis on kindling reached Abbreviations: EEG-electroencephalogram, GST-generalized seizure-triggering threshold. 1 This work was supported by research grant NS-13227 from the National Institute of Neurological and Communicative Disorders and Stroke and by the Research Service of the Veterans Administration. We thank Ms. Susan Holm for her expert collaboration. 524 0014-4886/79/120524-09$02.00/O Copyright 0 1979 by Academic Press. Inc. All rights of reproduction in any form reserved