Differential effects of competitive and non-competitive N-methyl-D-aspartate antagonists on glucose use in the limbic system.

The effects on cerebral glucose utilisation of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP, a competitive N-methyl-D-aspartate (NMDA) receptor antagonist), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801, a non-competitive NMDA receptor antagonist) have been examined in conscious rats. Cerebral glucose utilisation was assessed quantitatively with 14C-2-deoxyglucose autoradiography. MK-801 (0.05-5 mg/kg, i.v.) markedly increased glucose use in a number of limbic brain areas such as the mamillary body, anterior thalamic nucleus, posterior cingulate cortex and hippocampus. CPP (3-30 mg/kg, i.v.), in contrast, effected minimal alterations in glucose use in the limbic system. The functional consequences in vivo, as reflected in local cerebral glucose use, of competitive blockade of the NMDA receptor differ markedly from blockade with non-competitive antagonists.