Effect of up-regulation of NMDA receptors on cerebral O 2 consumption and blood flow in rat

Abstract

We tested the hypothesis that cerebrocortical blood flow and O 2 consumption would be proportional to an up-regulated number of functional N-methyl- d-aspartate (NMDA) receptors. Previous work had shown a relationship between cerebral metabolism and NMDA receptor activity. We increased the specific binding to NMDA receptors in the cerebral cortex, from 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-19755, an NMDA receptor inhibitor, for 7 consecutive days (discontinued for 20 h before experiment). Twelve up-regulated (CGS treated) and 12 control rats were used in this study. Under isoflurane anesthesia and after topical stimulation of the right cerebral cortex with 10 −2 M NMDA, the blood flow ( 14C-iodoantipyrine method) increased from 98 ± 11 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 for 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, upregulated cortex. Similarly, O 2 consumption (cryomicrospectrophotometrically 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 animals, 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 increase is dependent on the number of NMDA receptors present.