Manipulation of endogenous adenosine affects seizure susceptibility

A₁ adenosine receptors in rat prepiriform cortex (PPC) play an important role in the inhibition of bicuculline methiodide (BMI)-induced convulsions. In the present study, we evaluated the manipulation of endogenous adenosine in this brain area as a strategy to effect seizure suppression. All compounds evaluated were unilaterally microinjected into the PPC. Focal administration of 5' NH₂5'dADO and dilazep were found to be highly efficacious as anticonvulsants with respective ED₅₀ values of 2.6 ± 0.8, and 5.6 ± 1.6 nmol. In contrast, 2'DCF was both less potent and less efficacious. These results suggest that accumulation of endogenous adenosine may contribute to seizure suppression, and that adenosine kinase and adenosine transport may play a pivotal role in the regulation of extracellular levels of adenosine in the CNS.