Neurobiological and Pharmacological Perspectives of D3 Receptors in Parkinson’s Disease

The discovery of the D3 receptor (D3R) subtypes of dopamine (DA) has generated an understandable increase in interest in the field of neurological diseases, especially Parkinson’s disease (PD). Indeed, although DA replacement therapy with l-DOPA has provided an effective treatment for patients with PD, it is responsible for invalidating abnormal involuntary movements, known as L-DOPA-induced dyskinesia, which constitutes a serious limitation of the use of this therapy. Of particular interest is the finding that chronic l-DOPA treatment can trigger the expression of D1R–D3R heteromeric interactions in the dorsal striatum. The D3R is expressed in various tissues of the central nervous system, including the striatum. Compelling research has focused on striatal D3Rs in the context of PD and motor side effects, including dyskinesia, occurring with DA replacement therapy. Therefore, this review will briefly describe the basal ganglia (BG) and the DA transmission within these brain regions, before going into more detail with regard to the role of D3Rs in PD and their participation in the current treatments. Numerous studies have also highlighted specific interactions between D1Rs and D3Rs that could promote dyskinesia. Finally, this review will also address the possibility that D3Rs located outside of the BG may mediate some of the effects of DA replacement therapy.