Cerebellar impairment following acute nontoxic administration of phenytoin in rat.

In awake paralyzed Wistar rats, the following effects of an acute nontoxic dose of phenytoin (PHT) on different parameters of cerebellar electrical activity were evaluated: spontaneous discharge rate of single Purkinje cells (P-cells), field potentials, and responses of P-cells generated by electrical stimulation of a forelimb nerve. Variations of the response of single neurons located in the inferior olive were also studied, in order to assess the effects of PHT on this precerebellar relay station. The drug was administered orally and plasma and cerebellar levels regularly estimated. The results indicate that an acute, nontoxic dose of PHT is associated with an increase of P-cell firing rate. This finding is supported by the analysis of the frequency distribution of interspike intervals, and by the field potentials, P-cell, and olivary responses induced by stimulation of a radial nerve. In addition, it was observed that the increase in P-cell firing was mainly depending upon a higher activity of the climbing fibers. The increase in the response of P-cells and olivary cells was correlated with plasma and cerebellar drug levels. The conclusion was reached that PHT increases the cerebellar cortical activity through two mechanisms: (a) by acting directly on the cerebellar P-cell; and (b) indirectly by acting on the origin of climbing fibers at the inferior olive nucleus.