Unraveling the Role of Dopamine Receptors In Vivo: Lessons from Knockout Mice

Dopamine exerts its action through membrane receptors that belong to the seven transmembrane domains (7TM) G protein-coupled receptor family. The dopamine receptor family is composed of five members, which have been divided into two subgroups: the D1-like family, which contains the D1 receptor (D1R) and D5R, and the D2-like family containing D2R, D3R, and D4R. This subdivision is based on pharmacological, biochemical, and structural properties. Nevertheless, the close pharmacological properties together with the common anatomical site of expression of these receptors have induced the interest for generating animal models with which to assess the function of each individual dopamine receptor in vivo. To date, there exist mutants for all five receptors, in particular using the knockout technology each dopamine receptor has been independently knocked out. In this chapter we will summarize major findings related to the contribution of each dopamine receptor in the control of physiological functions regulated by dopamine. Analyses of these mutants clearly show a preponderant role for dopamine D1R and D2R receptors in most dopamine-mediated effects. At the same time these mutants are also revealing more hidden functions for D3R, D4R, and D5R very likely in the modulation of D1R- and D2R-mediated signaling.