Because of no apparent changes in the striatal D1R levels (Shinotoh et al., 1993; Turjanski et al., 1997; Hurley et al., 2001) and other principal mediators of the D1R signaling cascades (Girault et al., 1989; Nishino et al., 1993) in patients with PD, the marked increase in the Gαolf protein levels in the striatonigral MSNs may be a principal cause for generating striatal D1R hypersensitivity to levodopa exposure in PD. This evidence concerns the gene DRD1 and Parkinson disease.