Effect of NMDA antagonists on the activity of glutaminase and aspartate aminotransferase in the developing rat cerebellum

Chronic treatment of rats from postnatal day 6 to 25 with drugs that intera ct with the N-methyl- D-aspartare (NMDA) receptor induced a differential ef fect on the activity of some enzymes involved in neurotransmitter synthesis . Two of these drugs ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cy clohepten-5, 10-imine hydrogen maleate (MK-801) and 3-(2-carboxypiperazin-4 -yl)propyl-1-phosphonic acid (CPP)) caused a marked reduction (20-40%) of g lutaminase and aspartate aminotransferase activity in the cerebellum. These changes were observed only at a very precise time of development (i.e. 10 to 19 postnatal day). The competitive antagonist, amino phosphonovaleric ac id (APV), did not affect any of the enzymes studied at all tested ages. Whe n animals were treated with NMDA only a slight, but significant, increase i n the activity of glutaminase was observed at 9-11 postnatal day only. Any of the agonists or antagonists tested significantly affected the activity o f lactate dehydrogenase as compared to control animals. Histologic observat ions of cerebella treated with the indicated drugs showed that only MK-801, and CPP to a lesser extent, induced a small reduction in the width of the internal granule layer. The body weight of animals treated with MK-801 was clearly reduced, but only in more mature rats (>16 postnatal day), when ani mals did not show any alteration in the enzymes tested. These results suppo rt the suggestion that presynaptic influences, particularly from glutamater gic neurons, are critical to promote cerebellar granule neurons differentia tion during critical periods of the cerebellar development. (C) 1999 ISDN. Published by Elsevier Science Ltd. All rights reserved.