Abstract
In the striatum, signaling through G protein-coupled dopamine receptors mediates motor and reward behavior, and underlies the effects of addictive drugs. The extent of receptor responses is determined by RGS9-2/Gβ5 complexes, a striatally enriched regulator that limits the lifetime of activated G proteins. Recent studies suggest that the function of RGS9-2/Gβ5 is controlled by the association with an additional subunit, R7BP, making elucidation of its contribution to striatal signaling essential for understanding molecular mechanisms of behaviors mediated by the striatum. In this study, we report that elimination of R7BP in mice results in motor coordination deficits and greater locomotor response to morphine administration, consistent with the essential role of R7BP in maintaining RGS9-2 expression in the striatum. However, in contrast to previously reported observations with RGS9-2 knockouts, mice lacking R7BP do not show higher sensitivity to locomotor-stimulating effects of cocaine. Using a striatum-specific knockdown approach, we show that the sensitivity of motor stimulation to cocaine is instead dependent on RGS7, whose complex formation with R7BP is dictated by RGS9-2 expression. These results indicate that dopamine signaling in the striatum is controlled by concerted interplay between two RGS proteins, RGS7 and RGS9-2, which are balanced by a common subunit, R7BP.
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Acknowledgements
We thank Dr William Simonds (NIH/NIDDKD) for the generous gift of anti- RGS7 and R7BP antibodies. This work was supported by NIH grants DA021743 (KAM), DA026405 (KAM), F31 DA024944 (GRA), NS047399 (GJG), F31 NS047399 (SD), MH061933 (KW), DA011806 (KW), DA019666 (MJT), and a McKnight Land-Grant Award (KAM).
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The authors declare that except for the income received from the primary employers and NIH grants listed in the ‘Acknowledgements’ section below no financial compensation has been received from any individual or corporate entity over the past 3 years of research or professional service that could be perceived as constituting a potential conflict of interest.
Supplementary Information accompanies the paper on the Neuropsychopharmacology website (http://www.nature.com/npp)
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Anderson, G., Cao, Y., Davidson, S. et al. R7BP Complexes With RGS9-2 and RGS7 in the Striatum Differentially Control Motor Learning and Locomotor Responses to Cocaine. Neuropsychopharmacol 35, 1040–1050 (2010). https://doi.org/10.1038/npp.2009.212
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DOI: https://doi.org/10.1038/npp.2009.212
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