On the basis of the relationship between the occupied sites by pramipexole, the distribution of D2 and D3 receptors and previous anatomical and functional reports on depression, it is reasonable to suggest that pramipexole may exert its antidepressive effects by activating D2R subfamily, especially the D3 receptor subtype, in these regions (prefrontal cortex, amygdala, and thalamus). The gene discussed is DRD2; the disease is major depressive disorder.