DIPHENYLHYDANTOIN POTENTIATES THE EEG AND BEHAVIORAL-EFFECTS INDUCED BY N-METHYL-D-ASPARTATE ANTAGONISTS IN RATS

The N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid recep tors are involved in the electrical and behavioural generalization of epileptiform activity within the brain. In rats, both competitive and non-competitive NMDA antagonists induce three dose-dependent stages of EEG patterns: 1) increase in cortical desynchronization periods; 2) i ncrease in amplitude of cortical high frequency (20-30 Hz), low voltag e (30-50 mu V) background activity; 3) appearance of cortical slow (2- 3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by stimulatory-depressive behavioural effects such as stereotypy (circlin g, head weaving) and ataxia. In the present study, the influence of th e prototypic anticonvulsant diphenylhydantoin (DPH) has been tested on the EEG and behavioural effects induced by the non-competitive NMDA a ntagonists phencyclidine (PCP) and dizocilpine (MK-801) and by the com petitive NMDA antagonist cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755). Even though DPH (up to 100 mg/kg IP) did not marked ly affect basal cortical EEG activity, at doses of 10-100 mg/kg IP it potentiated all the EEG effects induced by the NMDA antagonists. These data support involvement of NMDA neurotransmission in the pharmacolog ical effects of DPH.