Dopamine D-4 receptors: significance for molecular psychiatry at the millennium

Extraordinary progress has been made in the molecular, genetic, anatomical, and pharmacological characterization of dopamine D-4, receptors in animal and human brain. Clarification of the neurochemical and physiological roles of these cerebral receptors is emerging, Postmortem neuropathological stud ies have inconsistently linked D-4, receptors to psychotic disorders, and g enetic studies have failed to sustain conclusive associations between D-4, receptors and schizophrenia. However, associations are emerging between D-4 , receptors and other neuropsychiatric disorders, including attention defic it hyperactivity disorder, mood disorders, and Parkinson's disease, as well as specific personality traits such as novelty-seeking. Selective D-4, ago nists and antagonists have been developed as useful experimental probes, D- 4, antagonists, so far, have proved ineffective in treatment of schizophren ia, but testing in a broader range of disorders may yield clinically useful drugs, D-4, receptors appear to have broad implications for the pathophysi ology of neuropsychiatric illnesses and their improved treatment.