The involvement of D-1 and D-2 dopamine (DA) receptors in mediating the DA regulation of preprotachykinin (PPT) gene expression was investigated in rat striatal tissue. Initial experiments determined that acute treatment with the indirect DA agonist methamphetamine induces increases in total PPT messenger RNA, with a maximal effect seen within 3 hr. RNA protection studies established that acute methamphetamine treatment did not affect the relative ratios of the various PPT gene transcripts derived by alternate splicing. The methamphetamine-induced increase in total PPT messenger RNA could be blocked by either a D-1 or a D-2 selective DA antagonist (SCH 23390 and sulpiride, respectively). The D-2 agonist quinpirole, but not the D-1 agonist SKF 38393, mimicked the methamphetamine-induced increase. This D-2 agonist-induced increase was dependent upon D-1 receptor tone, as either co-administration of SCH 23390 or pretreatment with the DA synthesis inhibitor alpha-methyltyrosine blocked the quinpirole-induced increase. These studies provide biochemical evidence for an enabling role of D-1 DA receptors in striatal D-2 DA receptor function.