LONG-TERM HALOPERIDOL ELEVATES DOPAMINE D-4 RECEPTORS BY 2-FOLD IN RATS

Chronic treatment of rats with neuroleptics results in elevated numbers of dopamine D-2-like receptors. The present study was done to determine whether neuroleptics altered the density of one type of dopamine D-2-like receptors, namely the dopamine D-4 receptor. We here describe the effect of a one-month treatment with haloperidol on dopamine D-4 receptor mRNA and protein levels in rat striatum. Endogenous levels of dopamine D-4 receptor mRNA in rat striatum are very low and, therefore, reverse transcription and subsequent amplification were used for quantification. Dopamine D-4 receptor density was, because of the absence of a dopamine D-4 receptor specific [H-3]ligand, determined by the difference between the number of binding sites for [H-3]nemonapride and [H-3]raclopride. Scatchard analysis of [H-3]nemonapride and [H-3]raclopride binding show that treatment for one month with haloperidol elevates the density of dopamine D-4 receptors in rat striatum by approximately 2-fold, whereas dopamine D-2 and D-3 receptors together show a 19% higher receptor density. Dopamine D-4 receptor mRNA was also approximately increased by 2-fold.