N-methyl-D-aspartate receptor antagonism alters substance P and met5-enkephalin biosynthesis in neurons of the rat striatum.

A reduction of striatal excitatory amino acids or of corticostriatal axons alters substance P (SP) and met5-enkephalin (ME) biosynthesis in striatal neurons of the rat. To determine the role of the N-methyl-D-aspartate (NMDA) receptor in this effect, adult rats were treated acutely with a single i.c.v. injection or chronically by 7 days of continuous infusion of an NMDA antagonist. The striatal content of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA was assessed by in situ hybridization histochemistry while the content of SP and ME in, respectively, the substantia nigra and globus pallidus was measured by quantitative radioimmunocytochemistry. Eight hours after a single injection, striatal PPT and PPE mRNA levels were significantly reduced. At 24 hr, the level of PPE had returned to control level whereas that of PPT mRNA remained depressed. Nigral SP and pallidal ME levels were not acutely changed. Chronically, the effect of NMDA antagonist at low doses was to increase the striatal content of PPE mRNA. However, at higher concentrations, the effect was to reduce in a dose-dependent manner the striatal content of PPT and PPE mRNA and the level of pallidal ME. The nigral level of SP did not change significantly at any dose. The results suggest that excitatory amino acid transmission mediated by the NMDA receptor serves as a tonic signal to stimulate neuroactive peptide biosynthesis.