Correlations between cerebellar activity and chronic nontoxic administration of phenytoin in rats.

The effect of long-term nontoxic treatment with phenytoin on the cerebellar Purkinje cell activity as determined by simultaneous monitoring of plasma and cerebellar levels of the drug has been studied in rats for the first time. The electrophysiological observations allowed the analysis of the spontaneous firing rate of the Purkinje cells and of the cerebellar field potentials generated by electrical stimulation of the ipsilateral radial nerve. The responses of single Purkinje cells to radial nerve stimulation were studied by constructing poststimulus time histograms and cumulative frequency distributions. The chronic treatment with phenytoin, which did not induce motor impairment or cerebellar symptoms, modified the firing rate of the Purkinje cells and the two modalities of Purkinje cell activation. In fact, phenytoin decreased significantly the spontaneous activity of the Purkinje cells and modified the strength of the mossy and climbing afferents.