Locomotor-activity-induced changes in striatal levels of preprotachykinin and preproenkephalin mRNA. Regulation by the dopaminergic and glutamatergicsystems

The mechanisms by which dopaminergic and glutamatergic inputs interact to r egulate striatal neuropeptide expression during physiological motor activit y are poorly understood. In this work, striatal expression of preprotachyki nin (PPT) and preproenkephalin (PPE) mRNA was studied by in situ hybridizat ion in rats killed 2 h after treadmill running (36 m/min for 20 min). Tread mill running induced a significant increase in the levels of both PPT (60% increase) and PPE (90% increase) mRNA in the striatum of normal rats. The i ncrease in the level of PPT mRNA was blocked in rats previously subjected t o nigrostriatal deafferentation (i.e., 6-hydroxydopamine lesion) or pretrea ted with D-1-receptor antagonist SCH-23390 (0.1 mg/kg), the D-2-receptor an tagonist eticlopride (0.5 mg/kg), or the N-methyl-D-aspartate (NMDA) glutam ate receptor antagonist MK-801(0.1 mg/kg). The running-induced increase in the level of PPE mRNA was blocked in rats pretreated with SCH-23390 or MK-8 01. Rats subjected to nigrostriatal deafferentation or pretreated with etic lopride showed an increase in PPE mRNA levels (around 150% and 40% increase , respectively), that was enhanced by running (around 230% and 160% increas e, respectively). These results suggest that locomotor activity increases, in a NMDA receptor dependent fashion, the excitatory influence of the corti costriatal glutamatergic system on the two populations of striatal projecti on neurons, as reflected by increases in the levels of PPT and PPE mRNA. Th e results obtained after dopamine depletion or injection of dopamine recept or antagonists suggest theta concomitant increase in dopamine release may e nhance PPT mRNA level in striatonigral neurons via D-1 receptors, and reduc e PPE mRNA level in striatopallidal neurons via D-2 receptors. Additionally , levels of dopamine and glutamate may be regulated by other complex indire ct mechanisms, (C) 1999 Elsevier Science B.V. All rights reserved.