Lesions of mouse striatum induced by 6-hydroxydopamine differentially alter the density, rate of synthesis, and level of gene expression of D1 and D2 dopamine receptors.

Abstract

To study the effects of altering dopaminergic input on the levels and rate of synthesis of dopamine receptors, corpora striata of mice were lesioned unilaterally with 6-hydroxydopamine (6-OHDA), and the densities and levels of the mRNAs for D1 and D2 dopamine receptors were determined. The results showed that 6-OHDA caused significant reductions in D1 dopamine receptors and in D1 dopamine receptor mRNA in dorsolateral and dorsomedial regions of the lesioned striatum. By contrast, 6-OHDA lesions caused significant increases in D2 dopamine receptors and in D2 dopamine receptor mRNA in dorsolateral and ventrolateral regions of the lesioned striatum. To assess the effects of 6-OHDA lesions on the rate of synthesis of D1 and D2 dopamine receptors, the irreversibly acting dopamine receptor antagonist 2-ethoxy-1-ethoxycarbonyl-1,2- dihydroquinoline (EEDQ) was administered, and the rate of recovery of these receptors determined. The lesions decreased the rate of synthesis of D1 dopamine receptors in dorsolateral striatum but increased the rate of synthesis of D2 dopamine receptors in dorsolateral striatum. Correlation of these molecular events with dopaminergic behaviors showed that the rate of recovery from EEDQ-induced cataleptic activity and the recovery from inhibition of quinpirole-induced rotational behavior was more rapid than the recovery of either the D1 or D2 dopamine receptor. These results suggest that dopaminergic denervation differentially affects the rate of synthesis of D1 and D2 dopamine receptors in mouse striatum, and that these alterations in the rates of synthesis of the receptors may be explained by corresponding alterations in the levels of the respective transcripts for these receptors.