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

Publication ,  Journal Article
Gainetdinov, RR; Bohn, LM; Sotnikova, TD; Cyr, M; Laakso, A; Macrae, AD; Torres, GE; Kim, KM; Lefkowitz, RJ; Caron, MG; Premont, RT
Published in: Neuron
April 24, 2003

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.

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Published In

Neuron

DOI

ISSN

0896-6273

Publication Date

April 24, 2003

Volume

38

Issue

2

Start / End Page

291 / 303

Location

United States

Related Subject Headings

  • Receptors, Dopamine D2
  • Receptors, Dopamine D1
  • Protein Serine-Threonine Kinases
  • Phosphoproteins
  • Phenethylamines
  • Neurons
  • Neurology & Neurosurgery
  • Nerve Tissue Proteins
  • Motor Activity
  • Mice, Mutant Strains
 

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Gainetdinov, R. R., Bohn, L. M., Sotnikova, T. D., Cyr, M., Laakso, A., Macrae, A. D., … Premont, R. T. (2003). Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice. Neuron, 38(2), 291–303. https://doi.org/10.1016/s0896-6273(03)00192-2
Gainetdinov, Raul R., Laura M. Bohn, Tatyana D. Sotnikova, Michel Cyr, Aki Laakso, Alexander D. Macrae, Gonzalo E. Torres, et al. “Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice.Neuron 38, no. 2 (April 24, 2003): 291–303. https://doi.org/10.1016/s0896-6273(03)00192-2.
Gainetdinov RR, Bohn LM, Sotnikova TD, Cyr M, Laakso A, Macrae AD, et al. Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice. Neuron. 2003 Apr 24;38(2):291–303.
Gainetdinov, Raul R., et al. “Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice.Neuron, vol. 38, no. 2, Apr. 2003, pp. 291–303. Pubmed, doi:10.1016/s0896-6273(03)00192-2.
Gainetdinov RR, Bohn LM, Sotnikova TD, Cyr M, Laakso A, Macrae AD, Torres GE, Kim KM, Lefkowitz RJ, Caron MG, Premont RT. Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice. Neuron. 2003 Apr 24;38(2):291–303.
Journal cover image

Published In

Neuron

DOI

ISSN

0896-6273

Publication Date

April 24, 2003

Volume

38

Issue

2

Start / End Page

291 / 303

Location

United States

Related Subject Headings

  • Receptors, Dopamine D2
  • Receptors, Dopamine D1
  • Protein Serine-Threonine Kinases
  • Phosphoproteins
  • Phenethylamines
  • Neurons
  • Neurology & Neurosurgery
  • Nerve Tissue Proteins
  • Motor Activity
  • Mice, Mutant Strains