[Functional role of dopamine D3 receptor in schizophrenia].
Since D3 receptors are highly localized in the limbic brain, which is closely linked to the positive symptoms of schizophrenia and cognition or emotional functions of the brain, the role of D3 receptors on schizophrenia has been intensively studied. Although a part of the D3 receptors acts as an autoreceptor, a majority of the autoreceptor function is attributed to D2 receptors, and D3 receptors play only a modulatory role. Relatively selective D3 agonists and antagonists showed an opposite effect between low and high dose. This phenomenon is explained by the fact that these drugs act on D3 receptors at a low dose but also on D2 receptors at a high dose. Although most antipsychotics have moderate affinities to D3 receptors, no consistent results were obtained on the effects of chronic administration of antipsychotics on D3 receptors. No consistent findings were reported on the D3 receptors in the postmortem brain of the schizophrenic. Recent meta-analysis studies showed a weak but significant association between D3 receptor polymorphism and schizophrenia. These studies suggest that the antipsychotics with some antagonistic profiles to D3 receptors can be promising atypical antipsychotics, which cause no prolactin secretion or extrapyramidal side effects.
Semba
Jun'ichi
J
University of the Air, Division of Health Sciences, 2-11, Wakaba, Mihama-ku, Chiba, 261-8586 Japan.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017660:Autoreceptors; D003071:Cognition; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004644:Emotions; D006801:Humans; D008032:Limbic System / Q000378:metabolism; D015201:Meta-Analysis as Topic; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000502:physiology; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology*
D014150:Antipsychotic Agents; D017660:Autoreceptors; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3