Selective deletion of GRK2 alters psychostimulant-induced behaviors and dopamine neurotransmission.

Journal Article (Journal Article)

GRK2 is a G protein-coupled receptor kinase (GRK) that is broadly expressed and is known to regulate diverse types of receptors. GRK2 null animals exhibit embryonic lethality due to a severe developmental heart defect, which has precluded the study of this kinase in the adult brain. To elucidate the specific role of GRK2 in the brain dopamine (DA) system, we used a conditional gene knockout approach to selectively delete GRK2 in DA D1 receptor (D1R)-, DA D2 receptor (D2R)-, adenosine 2A receptor (A2AR)-, or DA transporter (DAT)-expressing neurons. Here we show that select GRK2-deficient mice display hyperactivity, hyposensitivity, or hypersensitivity to the psychomotor effects of cocaine, altered striatal signaling, and DA release and uptake. Mice with GRK2 deficiency in D2R-expressing neurons also exhibited increased D2 autoreceptor activity. These findings reveal a cell-type-specific role for GRK2 in the regulation of normal motor behavior, sensitivity to psychostimulants, dopamine neurotransmission, and D2 autoreceptor function.

Full Text

Duke Authors

Cited Authors

  • Daigle, TL; Ferris, MJ; Gainetdinov, RR; Sotnikova, TD; Urs, NM; Jones, SR; Caron, MG

Published Date

  • September 2014

Published In

Volume / Issue

  • 39 / 10

Start / End Page

  • 2450 - 2462

PubMed ID

  • 24776686

Pubmed Central ID

  • PMC4138757

Electronic International Standard Serial Number (EISSN)

  • 1740-634X

Digital Object Identifier (DOI)

  • 10.1038/npp.2014.97


  • eng

Conference Location

  • England