CHRONIC THEOPHYLLINE PROLONGS THE REFRACTORY PERIOD IN AMYGDALA-KINDLED RATS

The effects of chronic theophylline treatment on brain adenosine A1 re ceptors and amygdala-kindled seizures were examined in rats. The repea ted administration of theophylline 417 mumoles/kg/day i.p. (75 mg/kg/d ay) for 14 days resulted in a significant increase in 1 nM [H-3]cycloh exyladenosine binding to adenosine A1 receptors in thalamus, hippocamp us, and cerebellum. This chronic theophylline treatment was shown to s ignificantly prolong the immediate postseizure refractory period (defi ned as sensitivity to a subsequent kindling stimulation) while both th e severity and duration of an initial kindled seizure was not affected . These findings indicate that the postseizure refractory period can b e influenced by the brain adenosine system, and implicate adenosine as an important neuromodulator of the patterning of seizure episodes. (C ) 1993 Wiley-Liss, Inc.