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The Journal of Neuroscience, 0000, 20:RC91:1-5

RAPID COMMUNICATION
G_OLF Mediates Dopamine D₁ Receptor Signaling

Xiaoxi Zhuang, Leonardo Belluscio, and Rene Hen

Center for Neurobiology and Behavior, Columbia University, New York, New York 10032

It is generally assumed that the coupling of dopamine D₁ receptors to adenylyl cyclase is mediated by the stimulatory GTP-binding protein G_s. However, the striatum contains little G_s subunit, whereas it expresses high levels of G_olf, a close relative of G_s that is also expressed in olfactory receptor neurons. We used G_olf knockout mice to examine the functional coupling of D₁ receptors. We found that these mice showed no hyperlocomotor response to either the D₁ agonist SKF-81297 or the psychostimulant cocaine. Moreover, G_olf knockout mice did not display cocaine-induced c-fos expression in the striatum. Finally, in the absence of G_olf, striatal D₁ receptors have a decreased affinity for dopamine. Thus coupling to G_olf appears to mediate D₁ signaling in the striatum.

Key words: dopamine; D₁ receptor; G_olf; G_s; striatum; knockout

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Copyright © 0000 Society for Neuroscience  0270-6474/00/$05.00/0

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