INCREASE OF ATP LEVELS BY GLUTAMATE ANTAGONISTS IS UNRELATED TO NEUROPROTECTION

SUCCINIC dehydrogenase in mouse cortical explant cultures was inhibite d by 3-nitropropionic acid (3-NPA). ATP concentrations declined upon a pplication of 3-NPA. At 4 h, ATP levels of cultures treated with 3-NPA alone were no different from those in cultures treated additionally w ith MK-801 (20 mu M), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 m u M) or a combination thereof. However, MK-801 and MK-801 plus CNQX mi tigated morphological lesions caused by 3-NPA. CNQX alone did not infl uence the extent of morphological damage. In conclusion, MK-801, at co ncentrations which were neuroprotective against 3-NPA lesions in corti cal explant cultures, did not modify 3-NPA dependent decreases in cell ular ATP levels. These data indicate that the neuroprotective effects of glutamate receptor antagonists in this model are probably receptor mediated and do not involve effects on cellular metabolism.