Long-term haloperidol elevates dopamine D 4 receptors by 2-fold in rats

Abstract

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 [ 3H]ligand, determined by the difference between the number of binding sites for [ 3H]nemonapride and [ 3H]raclopride. Scatchard analysis of [ 3H]nemonapride and [ 3H]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.