ANTAGONISTS OF N-METHYL-D-ASPARTATE RECEPTORS BLOCK SEIZURES INDUCED BY PUTRESCINE IN THE DEEP PREPIRIFORM CORTEX

The role of excitatory amino acid receptors in the genesis of motor and electrocortical seizures, elicited by administration of the polyamine putrescine into the deep prepiriform cortex, has been evaluated in rats. Motor and electrocortical seizures occurred in rats receiving unilateral local injections into the deep prepiriform cortex, of putrescine (10 or 20 nmol). The selective N-methyl-D-aspartate receptor antagonist, 2-amino-7-phosphonoheptanoate (AP7), injected previously (15 min) into the deep prepiriform cortex, prevented the development of seizures induced by putrescine, injected at the same site. In addition, dizocilpine (MK-801), a non-selective NMDA antagonist or ifenprodil, a specific inhibitor of the polyamine site at the NMDA receptor, when injected into the deep prepiriform cortex, 15 min prior to putrescine, significantly protected against seizures elicited by this polyamine. A subconvulsant dose of putrescine (5 nmol) potentiated the convulsant effects of NMDA, when injected into the deep prepiriform cortex. These data indicate a potential role of polyamines in the genesis of seizures, elicited from the deep prepiriform cortex. They further suggest that activation of the polyamine site, located at excitatory amino acid NMDA receptors, within the deep prepiriform cortex, may contribute to the genesis of seizure activity in this area.