Acute and subchronic effects of dopamine agonists on neuropeptide gene expression in the rat striatum

Abstract

Acute and subchronic (7 days) effects of subcutaneous administration of the D-1 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 pergolide (0.5 mg/kg) on enkephalin and substance P gene expression in the striatum were studied in rats using in situ hybridization. Striatal enkephalin mRNA levels were unaffected by acute dopamine agonist treatment despite animals exhibiting altered motor behaviour. Only acute apomorphine treatment increased substance P mRNA (25%, p <0.01). Following 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 following subchronic pergolide treatment (35%, p < 0.05). These data suggest that peptide gene expression in the intact striatum is relatively resistent to intermittent dopamine agonist stimulation in contrast to the pronounced alterations previously observed in 6-hydroxydopamine lesioned rats or following blockade of dopamine receptors.