Changes in GRK3/2 Levels in Brain Regions of Learned Helpless and Non‐Helpless Rats

• Published in: The FASEB journal 2008-04, Vol.22 (S2), p.613-613
• Main Authors: Taneja, Manish, Salim, Samina, Happe, H. Kevin, Petty, Frederick, Bylund, David B., Eikenburg, Douglas C.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.22.2_supplement.613

G protein‐coupled receptor kinases (GRKs) participate in the cellular adaptation to stress by phosphorylating G protein‐coupled receptors (GPCR), causing GPCR desensitization. GRK3 levels in neurons are increased by the stress hormones epinephrine and corticotropin releasing factor (CRF) but are reduced by oxidative stress. The desensitization of CRF1 receptors and alpha2‐adrenoceptors (α2‐AR), both involved in stress signaling in the brain and the development of depression, is preferentially regulated by GRK3. When rats are subjected to repeated unavoidable stress some develop Learned Helplessness (LH) behavior, considered a model of depression, while others display Non‐Helpless (NH) behavior. The present study was undertaken to determine the effects of repeated stress on GRK3 and GRK2 in several brain regions involved in the response to stress. Also studied were tested control rats not subjected to stress (TC). Proteins were measured in homogenates of brain regions by western blot analysis. In locus coeruleus (LC), GRK3 and GRK2 were decreased by 28% and 13%, respectively, and tyrosine hydroxylase (TH) was increased by 28% in LH rats as compared to NH and TC rats. In cortex, GRK3 was decreased by 30 and 33%, respectively, in LH and NH as compared to TC while GRK2 was decreased by 18% compared to TC. In hypothalamus and cerebellum, no changes were observed. The data suggest that GRK3 levels are significantly reduced in LC only in rats that develop LH. The reduced GRK3 levels in LC during development of LH may contribute to important changes in CRF1 and α2‐AR signaling in LC. (Supported by NARSAD, MH077224 and VA Merit Review)