Blockade of NMDA (N-methyl-D-aspartate) receptors for 5 h with MK 801 resulted in elevated levels of proenkephalin mRNA (up to 40% above vehicle-injected controls) in medial and anterior aspects of the caudate-putamen (mCPU and aCPU) and the nucleus accumbens (NAc). Increases were dose-dependent, with maximal effect at 0.1 mg/kg (body weight). These results suggest that NMDA receptor activity exerts tonic inhibition on proenkephalin mRNA expression in the striatum and accumbens of the rat brain.