Evidence for N-methyl-D-aspartate receptor-mediated increase in norepinephrine utilization in the prefrontal cortex of unanesthetized rats.

Local injection of N-methyl-D-aspartate (NMDA; 10-20 nmol/rat) into the prefrontal cortex of conscious rats caused a dose-related and an NMDA antagonist-reversible facilitation of norepinephrine (NE) disappearance in the cortical region during 35 min after inhibition of tyrosine hydroxylase. Destruction of ascending NE neurons by bilateral application of 6-hydroxydopamine into the superior cerebellar peduncle failed to affect [3H]N-(1-[2-thienyl]cyclohexyl)piperidine binding to the NMDA receptor-associated ion channel in the prefrontal cortex. These results indicate that, under unanesthetized conditions, the prefrontal NE neurons may be under glutamatergic facilitatory control mediated by the NMDA receptors which are located on the non-NE systems in the frontal cortex.