Assessment of dopamine D3 receptor function using D3 receptor knockout mice

It has been nearly a decade since distinct dopamine (DA) receptor subtypes began to be identified and cloned. Yet, the functional relevance of individual receptor subtypes remains poorly understood. This is particularly true for the "novel" receptors. For example, DA D3 receptors (D3Rs) have been proposed to exert a variety of important influences on both normal and abnormal behavioral processes. Early pharmacologic and localization studies fueled speculation that the DA D3R might play important roles in the etiology and treatment of schizophrenia. In rodents, activation of this receptor has been postulated to produce suppression of spontaneous locomotor activity and the induction of hypothermia, yawning and sniffing. More recently, a large body of evidence suggests that DA D3Rs exert negative feedback on DA neurons. However, due to the lack of selective ligands for this receptor, these ideas have been difficult to assess experimentally and the roles of DA D3Rs remain enigmatic. In an effort to evaluate the above hypotheses more directly, we utilized mice lacking the DA D3R. The focus of the present discussion is to relate the data acquired from DA D3R mutant (or 'knockout') mice to what has been reported previously using conventional pharmacologic methods.