Dopamine D4 receptors: significance for molecular psychiatry at the millennium.

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.