G(olf alpha) mediates dopamine D-1 receptor signaling

It is generally assumed that the coupling of dopamine D-1 receptors to aden ylyl cyclase is mediated by the stimulatory GTP-binding protein G(s). Howev er, the striatum contains little G(s alpha) subunit, whereas it expresses h igh levels of G(olf alpha), a close relative of G(s alpha) that is also exp ressed in olfactory receptor neurons. We used G(olf alpha) knockout mice to examine the functional coupling of D-1 receptors. We found that these mice showed no hyperlocomotor response to either the D-1 agonist SKF-81297 or t he psychostimulant cocaine. Moreover, G(olf alpha) knockout mice did not di splay cocaine-induced c-fos expression in the striatum. Finally, in the abs ence of G(olf alpha), striatal D-1 receptors have a decreased affinity for dopamine. Thus coupling to G(olf alpha) appears to mediate D-1 signaling in the striatum.