The Dopamine D3 Receptor: A Therapeutic Target for the Treatment of Neuropsychiatric Disorders

The role of the D3 receptor has remained largely elusive before the development of selective research tools, such as selective radioligands, antibodies, various highly specific pharmacological agents and knock-out mice. The data collected so far with these tools have removed some of the uncertainties regarding the functions mediated by the D3 receptor. The D3 receptor is an autoreceptor that controls the phasic, but not tonic activity of dopamine neurons. The D3 receptor, via regulation of its expression by the brain-derived neurotrophic factor (BDNF), mediates sensitization to dopamine indirect agonists. This process seems responsible for side-effects of levodopa (dyskinesia) in the treatment of Parkinson's disease (PD), as well as for some aspects of conditioning to drugs of abuse. The D3 receptor mediates behavioral abnormalities elicited by glutamate/NMDA receptor blockade, which suggests D3 receptor-selective antagonists as novel antipsychotic drugs. These data allow us to propose novel treatment options in PD, schizophrenia and drug addiction, which are awaiting evaluation in clinical trials.