Neurobiological studies of experimental diphenylhydantoin intoxication. II. Electrophysiological and electron microscopic studies of the rat cerebellum with chronic diphenylhydantoin intoxication.

The oral administration of diphenylhydantoin (DPH) for a period of more than nine months produced ataxia and muscle weakness in rats. The cerebellum of rats which were fed food containing DPH for a period of 12 months was studied electrophysiologically and morphologically. In the DPH-administered rats, little facilitation of Purkinje cell responses was elicited by the stimulation of the inferior olive, and a low frequency and a short duration of after-discharges on the cessation of tetani were observed as compared with that of the control rats. The value of the chronaxie of Purkinje cell axons was smaller in the DPH-administered rats than that in the control rats. Withdrawal of an overdose of DPH from the body returned these phenomena to those observed under normal condition, leaving the degeneration of synaptic boutons and some myelinated axons in the cerebellum. The electrophysiological results were well supported by the electron microscopic findings of degenerative presynaptic terminals and the depletion of synaptic vesicles.