Dopamine D₄ receptors: significance for molecular psychiatry at the millennium

Abstract

Extraordinary progress has been made in the molecular, genetic, anatomical, and pharmacological characterization of dopamine D₄ receptors in animal and human brain. Clarification of the neurochemical and physiological roles of these cerebral receptors is emerging. Postmortem neuropathological studies have inconsistently linked D₄ receptors to psychotic disorders, and genetic studies have failed to sustain conclusive associations between D₄ receptors and schizophrenia. However, associations are emerging between D₄ receptors and other neuropsychiatric disorders, including attention deficit hyperactivity disorder, mood disorders, and Parkinson's disease, as well as specific personality traits such as novelty-seeking. Selective D₄ agonists and antagonists have been developed as useful experimental probes. D₄antagonists, so far, have proved ineffective in treatment of schizophrenia, but testing in a broader range of disorders may yield clinically useful drugs. D₄ receptors appear to have broad implications for the pathophysiology of neuropsychiatric illnesses and their improved treatment.