ACUTE AND SUBCHRONIC EFFECTS OF DOPAMINE AGONISTS ON NEUROPEPTIDE GENE-EXPRESSION IN THE RAT STRIATUM

Acute and subchronic (7 days) effects of subcutaneous administration o f the D-l agonist (SKF 38393; 5.0 mg/kg), the D-2 agonist (quinpirole; 5.0 mg/kg), the mixed D-1/D-2 agonist (apomorphine; 5.0 mg/kg) or per golide (0.5 mg/kg) on enkephalin and substance P gene expression in th e striatum were studied in rats using in situ hybridization. Striatal enkephalin mRNA levels were unaffected by acute dopamine agonist treat ment despite animals exhibiting altered motor behaviour. Only acute ap omorphine treatment increased substance P mRNA (25%, p < 0.01). Follow ing subchronic administration of pergolide, enkephalin mRNA expression was decreased by 23% (p < 0.05) while other drugs were without effect . The abundance of striatal substance P mRNA was increased only follow ing subchronic pergolide treatment (35%, p < 0.05). These data suggest that peptide gene expression in the intact striatum is relatively res istent to intermittent dopamine agonist stimulation in contrast to the pronounced alterations previously observed in 6-hydroxydopamine lesio ned rats or following blockade of dopamine receptors.