Synergistic interaction between serotonin-2 receptor and dopamine D1 receptor stimulation on striatal preprotachykinin mRNA expression in the 6-hydroxydopamine lesioned rat

The regulation of striatal preprotachykinin (PPT) mRNA expression can be mediated through both dopamine (DA) D-1 and serotonin (5-HT) 5-HT2A/(2C) receptors. In the present study, we used in situ hybridization to examine possible synergistic interactions between 5-HT2A/(2C) and D-1 receptor-mediated regulation of striatal PPT mRNA levels in the rat depleted of DA with 6-hydroxydopamine. Acute administration of the 5-HT2A/(2C) receptor agonist DOI (2 mg/kg) significantly increased (+ 75%) PPT mRNA levels in the dorsal striatum. Acute administration of the D-1 receptor agonist SKF-38393 (2 mg/kg) did not significantly alter PPT mRNA levels in the dorsal striatum. However, the co-administration of SKF-38393 and DOI produced a significant increase (+ 300%) in striatal PPT mRNA expression restricted to the periventricular region of the dorsal-medial striatum. This synergistic interaction was not observed in the remaining aspect of the dorsal striatum where DOI alone increased PPT mRNA expression. These data show that 5-HT2A/(2C) and D-1 receptors can act in a synergistic manner to regulate striatal PPT mRNA in a subregion of the DA-depleted striatum. (C) 1999 Elsevier Science B.V. All rights reserved.