| First Author | Daigle TL | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 33 | Pages | 11461-6 |
| PubMed ID | 22895728 | Mgi Jnum | J:187717 |
| Mgi Id | MGI:5437818 | Doi | 10.1523/JNEUROSCI.2234-12.2012 |
| Citation | Daigle TL, et al. (2012) Elimination of GRK2 from Cholinergic Neurons Reduces Behavioral Sensitivity to Muscarinic Receptor Activation. J Neurosci 32(33):11461-6 |
| abstractText | Although G-protein-coupled receptor kinase 2 (GRK2) is the most widely studied member of a family of kinases that has been shown to exert powerful influences on a variety of G-protein-coupled receptors, its role in the brain remains largely unknown. Here we report the localization of GRK2 in the mouse brain and generate novel conditional knock-out (KO) mice to assess the physiological importance of this kinase in cholinergic neurons. Mice with the selective deletion of GRK2 in this cell population (ChAT(IRES-cre)Grk2(f/f) KO mice) exhibit reduced behavioral responsiveness to challenge with oxotremorine-M (Oxo-M), a nonselective muscarinic acetylcholine receptor agonist. Specifically, Oxo-M-induced hypothermia, hypolocomotion, and salivation were markedly reduced in these animals, while analgesic responses were unaltered. In contrast, we found that GRK2 deficiency in cholinergic neurons does not alter cocaine-induced psychomotor activation, behavioral sensitization, or conditioned place preference. These results demonstrate that the elimination of GRK2 in cholinergic neurons reduces sensitivity to select muscarinic-mediated behaviors, while dopaminergic effects remain intact and further suggests that GRK2 may selectively impair muscarinic acetylcholine receptor-mediated function in vivo. |
