N-methyl-D-aspartate promotes the survival of cerebellar granule cells: pharmacological characterization

The survival of cerebellar granule cells in culture is promoted by chronic exposure to N-methyl-D-aspartate (NMDA). The effect is due to the stimulation of 'conventional' NMDA receptor-ionophore complex: it is concentration dependent, voltage dependent and blocked by the selective antagonists D-2-amino-5-phosphonovalerate, D-2-amino-7-phosphonoheptanoate, dextromethorphan and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imin emaleate (MK 801). The most potent antagonist tested was MK-801. In contrast, non-selective antagonists, including kynurenate, were much less effective. Further, the trophic effect of NMDA is not reproduced by ibotenate or quinolinate at the concentration range tested. It could also be shown that glutamate released into the culture medium is responsible for limited cell survival in the absence of NMDA.