Kainic acid (KA), microinjected unilaterally into the rat prepiriform cortex (PC), produces generalized motor seizures in a dose-dependent manner. The adenosine agonist N-ethylcarboxamidoadenosine (NECA), when co-injected with KA, protects against seizures in a dose-dependent and highly potent manner: ED50 = 25.6 +/- 2.1 pmol/rat. The seizure-suppressing effects of NECA are completely abolished by co-administration of the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (8-pSPT), suggesting that adenosine receptor activation underlies the efficacy of NECA against KA seizures. Moreover, dilazep, an effective blocker of adenosine uptake, when co-administered with KA, provides significant protection against seizures. Together, these findings suggest that adenosine receptors may play an important role in the regulation of the inhibitory neuronal circuitry of this paleocortical brain area.