Long-term effect of convulsive behavior on the density of adenosine A(1) and A(2A) receptors in the rat cerebral cortex

Purpose: Adenosine is a neuromodulator that has been proposed to act as an anticonvulsant mainly via inhibitory A, receptors, but recent data show that genetic deletion of facilitatory A(2A) receptors might also attenuate convulsions. Since both A(1) and A(2A), receptors are prone to down- and upregulation in different stressful situations, we investigated if convulsive behavior leads to a long-term change in A(1) and A(2A) receptor density in the rat cerebral cortex. Methods: Stage 4-5 convulsions (Racine's scale) were induced in adult Wistar rats either through amygdala stimulation (kindling) or by intraperitoneal injection of kainate (10 mg/ml). Rats were killed after 4 weeks to evaluate adenosine A(1) and A(2A) receptor density in the cerebral cortex using both Western blot and membrane binding assays. Results: The binding density of the A(1) antagonist, H-3-DPCPX, decreased by 40. +/- 4.4% and by 20.7 +/- 0.5% after kindling or kainate injection. Likewise, A, receptor immunoreactivity in cortical membranes from kindled or kainate-injected rats decreased by 19.1 3.3% and 12.7 5.7%, respectively. In contrast, the binding density of the A(2A) receptor antagonist 3 H-SCH 58261 increased by 293 34% and by 159 32% in cortical membranes from kindled or kainate-injected rats, and A(2A) receptor immunoreactivity also increased by 151 12% and 79.6 7.0%. Conclusions: This indicates that after convulsive behavior there is a long-term decrease of A, receptors accompanied by an increased density of A(2A) receptors, suggesting that A(2A) antagonists rather than A(1) agonists may be more promising anticonvulsive drugs.