THE D-3 DOPAMINE-RECEPTOR IN CELLULAR AND ORGANISMAL FUNCTION

The D-3 dopamine receptor is a member of the family of D-2-like dopami ne receptors. Since the cloning and identification of the D-3 receptor in 1990, considerable progress has been made towards understanding th e function of this novel site. Although some avenues of investigation have yielded more definitive results than others, studies to date indi cate the D-3 receptor is localized preferentially in limbic brain area s and affects locomotion and perhaps reinforcement and reward. A subpo pulation of the receptors appear to be autoreceptors which modulate do pamine synthesis, release, and neuronal activity. These observations h ave led to the hypothesis that the D-3 receptor may be an appropriate target in the treatment of neuropsychiatric disorders such as schizoph renia and drug addiction. The role of D-3 sites in disease, however, r emains to be established. Genetic association of D-3 receptor polymorp hisms with neuropsychiatric disorders have been proposed. Alterations in expression of Dg sites may occur in some diseases. Although the stu dy of this receptor is clearly in the early stages, these findings lay the foundation for future investigation. In this review, dopamine D-3 receptor brain localization, cellular signaling mechanisms, and assoc iated behavior will be discussed. The potential role of the D-3 site i n neuropsychiatric disorders and as a therapeutic target is also addre ssed.