Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice.

Journal Article (Journal Article)

Brain dopaminergic transmission is a critical component in numerous vital functions, and its dysfunction is involved in several disorders, including addiction and Parkinson's disease. Responses to dopamine are mediated via G protein-coupled dopamine receptors (D1-D5). Desensitization of G protein-coupled receptors is mediated via phosphorylation by members of the family of G protein-coupled receptor kinases (GRK1-GRK7). Here we show that GRK6-deficient mice are supersensitive to the locomotor-stimulating effect of psychostimulants, including cocaine and amphetamine. In addition, these mice demonstrate an enhanced coupling of striatal D2-like dopamine receptors to G proteins and augmented locomotor response to direct dopamine agonists both in intact and in dopamine-depleted animals. The present study indicates that postsynaptic D2-like dopamine receptors are physiological targets for GRK6 and suggests that this regulatory mechanism contributes to central dopaminergic supersensitivity.

Full Text

Duke Authors

Cited Authors

  • Gainetdinov, RR; Bohn, LM; Sotnikova, TD; Cyr, M; Laakso, A; Macrae, AD; Torres, GE; Kim, KM; Lefkowitz, RJ; Caron, MG; Premont, RT

Published Date

  • April 24, 2003

Published In

Volume / Issue

  • 38 / 2

Start / End Page

  • 291 - 303

PubMed ID

  • 12718862

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/s0896-6273(03)00192-2


  • eng

Conference Location

  • United States