Striatal tachykinin biosynthesis: regulation of mRNA and peptide levels by dopamine agonists and antagonists.

The effects of dopamine agonists and antagonists on rat basal ganglia substance P, substance K, and preprotachykinin mRNA were examined. Chronic administration of the prototypical dopamine antagonist haloperidol decreased striatal preprotachykinin mRNA and nigral tachykinin peptides. Chronic treatment with the dopamine D2 receptor antagonist L-sulpiride (but not the inactive D-isomer) mimicked the effect of haloperidol. In contrast, the atypical neuroleptic clozapine did not decrease tachykinin mRNA or peptides. The potent indirect dopamine agonist methamphetamine rapidly increased preprotachykinin mRNA, substance P, and substance K although the direct agonist apomorphine was without effect. Methamphetamine-stimulated changes in preprotachykinin mRNA were prevented by prior haloperidol administration. These data demonstrate that alterations in dopaminergic transmission significantly alter striatonigral tachykinin biosynthesis in vivo.