The mRNA levels encoding for the enzyme glutamate decarboxylase (GAD67) and the peptide enkephalin were measured in the striatum of adult and 15 day-old rats by in situ hybridization histochemistry and radioautography after neonatal injections of 6-hydroxydopamine or after acute pharmacological blockade of dopamine receptors with haloperidol or sulpiride. In adult rats injected as neonates with 6-hydroxydopamine or treated with the D1/D2 dopamine receptors antagonist, haloperidol, an increase in preproenkephalin and GAD67 mRNA levels was measured in the striatum. The D2 dopamine receptor antagonist, sulpiride, did not change the mRNA levels of either GAD67 or PPE in the striatum. In 15-day-old rats, neonatal 6-hydroxydopamine or haloperidol treatment resulted in increased preproenkephalin but unchanged GAD67 mRNA levels compared to controls. In these 15-day-old rats, however, sulpiride produced an increase in GAD67 but not preproenkephalin mRNA levels. Intrastriatal injections to adult rats of pertussis toxin which uncouples Gi/Go proteins from their receptors resulted in a dramatic increase in preproenkephalin without concomitant change in GAD67 mRNA levels. Altogether, these results show that GAD67 and preproenkephalin mRNA levels are modulated in parallel in adult but not in 15 day-old rats after 6-hydroxydopamine injections or dopaminergic blockade. In keeping with evidence of a co-localization of GAD67 and preproenkephalin mRNAs in some striatal neurons, the results indicate that these two mRNAs can be differentially regulated in the same neurons. In addition, the differential effect of haloperidol, sulpiride or pertussis toxin on GAD67 and preproenkephalin mRNA levels suggests that these two mRNAs are regulated through different dopamine receptor subtypes.