The compensatory downregulation of DAT in early PD is thought to maintain dopamine levels in the synapse.35 Zhang and Li have recently reported that DAT expression depends on the striatal extracellular dopamine concentration.36 The activation of σ1R through enhancing NMDAr can increase the dopamine release.7 Indeed, the application of NMDA in σ1R−/− mice could enhance the expression of DAT. This evidence concerns the gene SLC6A3 and Parkinson disease.