NMDA receptor antagonism modifies the synergistic regulation of striatal tachykinin gene expression induced by dopamine D(1) and serotonin(2) receptor stimulation following neonatal dopamine depletion.

摘要

Co-application of SKF-38393 (dopamine D(1) agonist; 1 mg/kg) and DOI (serotonin(2) agonist; 1 mg/kg) induced a synergistic increase in striatal preprotachykinin (PPT) mRNA levels in adult rats 60 days after neonatal intracerebroventricular injection of 6-hydroxydopamine. This magnitude of response was not observed in intact (vehicle-injected) rats and was restricted to the dorsomedial (DM, 333+/-25% of lesion) subregion of the anterior striatum, with smaller increases observed in the dorsolateral striatum (DL, 206+/-26% of lesion). A single i.p. injection of MK-801 (NMDA antagonist; 0.1 mg/kg) administered prior to dopamine D(1) (D(1)) and serotonin(2) (5-HT(2)) receptor co-stimulation suppressed the synergistic regulation of PPT mRNA expression in the DM striatum, but also produced a large increase in PPT message levels within the DL striatum (321+/-17% of lesion). These data suggest that the synergistic regulation of PPT mRNA within the DM striatum induced by D(1)/5-HT(2) receptor co-stimulation in the dopamine lesioned rat is dependent on NMDA receptor activity. However, MK-801 may simultaneously potentiate striatal PPT mRNA expression by a separate mechanism due to the changed environment of the dopamine-depleted basal ganglia.