METABOLITE LEVELS IN BRAIN FOLLOWING EXPERIMENTAL SEIZURES: THE EFFECTS OF MAXIMAL ELECTROSHOCK AND PHENYTOIN IN CEREBELLAR LAYERS

Abstract— The effects of maximal electroshock (MES) and phenytoin on metabolites and cyclic nucleotides in layers of frozen-dried cerebellum have been investigated. The four layers (molecular, Purkinje-cell rich, granular and white matter) had remarkably homogeneous distributions of P-creatine, ATP, glucose, glycogen, lactate, GABA and the cyclic nucleotides. MES caused dramatic decreases in P-creatine, ATP, and glucose at 10 s after treatment, followed by a decrease in glycogen at 30 s. Lactate levels were elevated, and GABA was unchanged. Cyclic AMP concentrations were increased at 10s and cyclic GMP at 30 s. Phenytoin modified most of the MES induced changes in all the layers, although white matter was less affected by MES and/or phenytoin. Lactate concentrations were increased by MES and these effects were not altered when phenytoin was administered. The most dramatic effects of phenytoin were on the changes in cyclic nucleotides. Cyclic AMP concentrations were elevated after MES but the values returned to normal more rapidly when phenytoin was present. The drug almost obliterated the MES induced changes in cyclic GMP. The possible relationship of cyclic nucleotide concentrations and the modulation of seizure activity is discussed.