Abstract
A compelling body of evidence suggests that endogenous adenosine may function as an inhibitory modulator of epileptogenesis. One brain area which appears to be fundamentally important to the initiation and expression of generalized motor seizures in the rat is the prepiriform cortex (PPC) (Piredda and Gale. Nature 317, 623, 1985). The protective effects of a series of adenosine analogs against generalized seizures initiated by focal injection of bicuculline methiodide (BMI) into the PPC was investigated by microinjection of these compounds into this brain area. The rank order potency of adenosine analogs in suppressing seizures was as follows： NECA > cyclohexyladenosine >cyclopentyladenosine > R- PIA > 2-chloroadenosine > S-PIA >>> CV1808. These data suggest that the antiseizure activity of these compounds in the PPC results from activation of A_1 adenosine receptors. The seizure suppressant effect of NECA was similarly manifest against kainic acid-induced seizures in the rat PPC. The sensitivity of kainic acid-and BMI-induced seizures to suppression by adenosine receptor activation in the PPC suggests that adenosine receptors may either directly regulate the activity of excitatory output neurons of this brain area and/or regulate excitatory afferents in the PPC.