Effects of diphenylhydantoin on the spontaneous activity of Purkinje, nucleus interpositus, red nucleus and motor cortex cells.

(1) Extracellular multiunit recordings were made of the spontaneous activity in cerebellar Purkinje cells, nucleus interpositus, red nucleus and sensorimotor cortex in acute cat preparations. (2) Changes in this spontaneous neural activity produced by the administration of diphyenylhydantoin (DPH) were studied. DPH was infused i.v., generally at a concentration of 2.5 mg/ml and at a rate varying from 0.08 to 0.48 mg/kg/min. Two different patterns of infusion were used: fixed time, variable rate and variable time, fixed rate. Pulsed doses were also given at intervals of 5--10 min. (3) DPH at a level of 10--20 mg/kg produces a significative initial deceleration in all structures followed by a significative acceleration in the Purkinje cells, nucleus interpositus and red nucleus as a dose of 20--30 mg/kg is reached. Higher levels caused a profound depression of multiunit activity. (4) The activation produced by DPH is oscillatory (3--5/min) in character and is composed of 'trains' which occur at a rate of 20--30/sec with very rapid discharge frequencies (600--800 Hz). (5) A direct significant correlation was found between DPH serum levels and the intravenously administered dose. The activating DPH dose (20--30 mg/kg) corresponded to serum levels of 24--32 micrograms/ml. (6) The possibility is discussed whether the anticonvulsant action of DPH may be due in part to the production of rhythmic oscillatory activity in the cerebello-rubro-olivo-cerebellar ciruit and the depression of the cerebellothalamic-cortical pathway.