EFFECT OF REPEATED ADMINISTRATION OF DOPAMINE AGONISTS ON STRIATAL NEUROPEPTIDE MESSENGER-RNA EXPRESSION IN RATS WITH A UNILATERAL NIGRAL 6-HYDROXYDOPAMINE LESION

Striatal mRNA expression for preproenkephalin (PPE) and preprotachykin in (PPT) was studied in unilateral 6-OHDA lesioned rats treated subchr onically with a range of selective and non-selective D-1 or D-2 dopami ne (DA) agonists. Apomorphine (5 mg/kg sc), pergolide (0.5 mg/kg sc), SKF 38393 (5 mg/kg sc), SKF 80723 (1.5 mg/kg sc), and quinpirole (5 mg /kg sc), or 0.9% saline (150 mu l sc) were all given twice daily (exce pt pergolide: once daily) for 7 days. The abundance of PPE mRNA was no t altered by any of these DA agonists in the intact striatum contralat eral to the 6-OHDA lesion. Only apomorphine and quinpirole increased t he abundance of PPT mRNA in the intact striatum. In saline treated 6-O HDA lesioned animals PPE mRNA was elevated (+160%, p < 0.005) and PPT mRNA decreased (-36%, p < 0.005) in the denervated striatum. The up-re gulation of striatal PPE mRNA in the lesioned striatum was reversed on ly by pergolide. The downregulation of striatal PPT mRNA in the lesion ed striatum was reversed only by apomorphine. The differential sensiti vity of the striatal PPE message to the long-acting DA agonist pergoli de, and of the striatal PPT message to the mixed D-1/D-2 DA agonist ap omorphine suggests that the striatopallidal enkephalinergic pathways a re mainly regulated by prolonged DA receptor stimulation, whereas the striatonigral substance P pathways are mainly regulated by mixed D-1/D -2 DA receptor stimulation.