Chronic theophylline prolongs the refractory period in amygdala-kindled rats

The effects of chronic theophylline treatment on brain adenosine A₁ receptors and amygdala-kindled seizures were examined in rats. The repeated administration of theophylline 417 μmoles/kg/day i.p. (75 mg/kg/day) for 14 days resulted in a significant increase in 1 nM [³H]cyclohexyladenosine binding to adenosine A₁ receptors in thalamus, hippocampus, and cerebellum. This chronic theophylline treatment was shown to significantly prolong the immediate postseizure refractory period (defined as sensitivity to a subsequent kindling stimulation) while both the severity and duration of an initial kindled seizure was not affected. These findings indicate that the postseizure refractory period can be influenced by the brain adenosine system, and implicate adenosine as an important neuromodulator of the patterning of seizure episodes.