Continuous treatment with the D 2 dopamine receptor agonist quinpirole decreases D 2 dopamine receptors, D 2 dopamine receptor messenger RNA and proenkephalin messenger RNA, and increases mu opioid receptors in mouse striatum

Abstract

Dopamine-mediated behaviors and certain biochemical and molecular events associated with these behaviors were examined following continuous infusion of the D 1dopamine agonist SKF38393 or the D 2dopamine agonist quinpirole into mice for six days. SKF38393 produced a transient grooming behavior while quinpirole initially induced stereotypy, which was followed by an increased locomotor behavior. Continuous infusion of quinpirole caused a significant down-regulation of striatal D 2dopamine receptors without significantly changing the density of D 1 receptors. This was accompanied by a decrease in the level of D 2 receptor messenger RNA in striatum as measured by Northern analysis. The down-regulation of dopamine receptors was selective for D 2 dopamine receptors, since treatment with SKF38393 had no significant effects on either D 1or D 2 dopamine receptors, nor did it alter the messenger RNAs for the D 1 and D 2 receptors. Continuous treatment with quinpirole resulted in a significant increase in striatal mu opioid receptor levels without significant changing delta opioid receptors. This treatment also induced a significant decrease in proenkephalin messenger RNA in striatum. Taken together, these results suggest that the down-regulation of D 2 dopamine receptor and D 2 receptor messenger RNA is the result of the persistent stimulation of D 2 receptors and that the up-regulation of mu opioid receptors may be a compensatory response to a decreased biosynthesis of enkephalin. They suggest further that the biochemical and molecular changes that take place in dopaminergic and enkephalinergic systems following continuous treatment with dopamine agonists may underlie the mechanisms by which certain dopamine-mediated behaviors occur.