ELEVATION OF STRIATAL AND ACCUMBAL PREPROENKEPHALIN, PREPROTACHYKININAND PREPRODYNORPHIN MESSENGER-RNA ABUNDANCE SUBSEQUENT TO N-METHYL-D-ASPARTATE RECEPTOR BLOCKADE WITH MK-801

The effect of N-methyl-D-aspartate (NMDA) receptor blockade on the exp ression of preproenkephalin (PPE), preprotachykinin (PPT) and preprody norphin (PPD) mRNAs in the caudate-putamen and nucleus accumbens was a ssessed with the non-competitive NMDA receptor antagonist MK-801. Admi nistration of MK-801 once daily for 7 consecutive days increased the a bundance of all three neuropeptide mRNAs in the caudate-putamen (CPU) and nucleus accumbens (NAc). (1) PPE mRNA abundance was increased in t he anterior CPU (26%) as well as dorsal and ventral CPU (46% and 39%, respectively) but was unaffected in the NAc. (2) PPT mRNA was increase d in the NAc (33%), anterior CPU (27%), dorsal CPU (43%) and ventral C PU (67%). In the ventral CPU, PPT mRNA abundance doubled when the dose of MK-801 increased two-fold (from 67% to 119% above control). (3) PP D mRNA was elevated in dorsal and ventral regions of the CPU (49% and 24%, respectively) and in anterior CPU (50%). In the NAc PPD mRNA was increased only at the higher dose (0.1 mg/kg) of MK-801. Cellular anal ysis of the distribution of grains per cell shows that increases are d ue to increased accumulation of mRNA by previously expressing cells of the CPU and NAc. These observations demonstrate that NMDA receptor ac tivity plays a significant role in the regulation of neuropeptide expr ession in the caudate-putamen and accumbens of the rat brain.