The D3 dopamine receptor in cellular and organismal function

Abstract

 The D₃ dopamine receptor is a member of the family of D₂-like dopamine receptors. Since the cloning and identification of the D₃ receptor in 1990, considerable progress has been made towards understanding the function of this novel site. Although some avenues of investigation have yielded more definitive results than others, studies to date indicate the D₃ receptor is localized preferentially in limbic brain areas and affects locomotion and perhaps reinforcement and reward. A subpopulation of the receptors appear to be autoreceptors which modulate dopamine synthesis, release, and neuronal activity. These observations have led to the hypothesis that the D₃ receptor may be an appropriate target in the treatment of neuropsychiatric disorders such as schizophrenia and drug addiction. The role of D₃ sites in disease, however, remains to be established. Genetic association of D₃ receptor polymorphisms with neuropsychiatric disorders have been proposed. Alterations in expression of D₃ sites may occur in some diseases. Although the study of this receptor is clearly in the early stages, these findings lay the foundation for future investigation. In this review, dopamine D₃ receptor brain localization, cellular signaling mechanisms, and associated behavior will be discussed. The potential role of the D₃ site in neuropsychiatric disorders and as a therapeutic target is also addressed.