INDOMETHACIN MODULATES ISCHEMIA-EVOKED RELEASE OF GLUTAMATE AND ADENOSINE FROM THE RAT CEREBRAL-CORTEX

The effects of indomethacin (10 mg/kg) on the release of the transmitt er amino acids, glutamate, aspartate, GABA, and of the purines, adenos ine and inosine, from the cerebral cortex was studied in a four-vessel occlusion rat model of cerebral ischemia/reperfusion. In comparison w ith the control group, indomethacin significantly attenuated the ische mia-evoked release of glutamate and aspartate, but not of GABA. Adenos ine levels in the cortical superfusates were significantly elevated fo llowing indomethacin administration. As indomethacin is a potent inhib itor of adenosine uptake, these results suggest that, by blocking aden osine uptake, indomethacin could elevate extracellular adenosine level s and depress glutamate and aspartate efflux as a consequence of the a ctivation of adenosine A(1) receptors.