D ₁ and D ₂ Dopamine Receptor-regulated Gene Expression of Striatonigral and Striatopallidal Neurons

TLDR

The striatum, a major basal ganglia component, is modulated by dopaminergic input from the substantia nigra, and loss of this input in Parkinson’s disease causes movement disorders; 6‑hydroxydopamine lesions in rats model these changes by altering gene expression in striatonigral and striatopallidal pathways. In 6‑OHDA‑treated rats, striatopallidal neurons upregulate D2 and enkephalin mRNAs, an effect reversed by the D2 agonist quinpirole, while striatonigral neurons downregulate D1 and substance P mRNAs, reversed by the D1 agonist SKF‑38393 and accompanied by increased dynorphin mRNA, demonstrating that dopamine’s differential effects are mediated by specific D1 and D2 receptor expression.

Abstract

The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D 2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D 2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D 1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D 1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D 1 and D 2 dopamine receptor subtypes, respectively.