The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders.
The role of the D(3) 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 D(3) receptor. The D(3) receptor is an autoreceptor that controls the phasic, but not tonic activity of dopamine neurons. The D(3) 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 D(3) receptor mediates behavioral abnormalities elicited by glutamate/NMDA receptor blockade, which suggests D(3) 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.
Sokoloff
P
P
INSERM, Unité de Neurobiologie et Pharmacologie, Moléculaire (U573), Centre Paul Broca, 2ter rue d'Alésia, 75014 Paris, France. pierre.sokoloff@pierre-fabre.com
Diaz
J
J
Le Foll
B
B
Guillin
O
O
Leriche
L
L
Bezard
E
E
Gross
C
C
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018491:Dopamine Agonists / Q000009:adverse effects; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D050637:Receptors, Dopamine D3