EFFECT OF UP-REGULATION OF NMDA RECEPTORS ON CEREBRAL O-2 CONSUMPTIONAND BLOOD-FLOW IN RAT

We tested the hypothesis that cerebrocortical blood flow and O-2 consu mption would be proportional to an up-regulated number of functional N -methyl-D-aspartate (NMDA) receptors. Previous work had shown a relati onship between cerebral metabolism and NMDA receptor activity. We incr eased the specific binding to NMDA receptors in the cerebral cortex, f rom 2.2 +/- 0.9 to 4.5 +/- 0.8 (density units) in male Long-Evans rats by daily giving two intraperitoneal injections (30 mg/kg) of CGS-1975 5, an NMDA receptor inhibitor, for 7 consecutive days (discontinued fo r 20 h before experiment). Twelve up-regulated (CGS treated) and 12 co ntrol rats were used in this study. Under isoflurane anesthesia and af ter topical stimulation of the right cerebral cortex with 10(-2) M NMD A, the blood flow (C-14-iodoantipyrine method) increased from 98 +/- 1 1 ml/min/100 g in the unstimulated cortex of the control rats to 161 /- 37 ml/min/100 g in the stimulated cortex. The unstimulated value fo r blood flow (95 +/- 7 ml/min/100 g) did not change in the upregulated group but it doubled (194 +/- 69 ml/min/100 g) in the stimulated, upr egulated cortex. Similarly, O, consumption (cryomicrospectrophotometri cally determined) in normal rats increased 46%, from 9.3 +/- 1 ml/min/ 100 g to 13.6 +/- 4 after NMDA stimulation. While in the upregulated a nimals, O-2 consumption increased 103% from 7.9 +/- 0.6 to 16 +/- 6.5 after NMDA stimulation. In conclusion, NMDA receptor upregulation does not alter basal cerebrocortical blood flow or O-2 consumption but in the NMDA-stimulated cortex, the blood flow and O-2 consumption increas e is dependent on the number of NMDA receptors present.