Differential effects of inescapable stress on locus coeruleus GRK3, alpha(2)-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: A potential link to stress resilience

作者：Taneja Manish; Salim Samina; Saha Kaustuv; Happe H Kevin; Qutna Nidal; Petty Frederick; Bylund David B; Eikenburg Douglas C^*

来源：Behavioural Brain Research, 2011, 221(1): 25-33.

DOI：10.1016/j.bbr.2011.02.018

• Learned helplessness
• GRK3
• Alpha(2A)-AR
• CRF1 receptor
• Stress
• Resilience

Exposure of rats to unpredictable, inescapable stress results in two distinct behaviors during subsequent escape testing. One behavior, suggestive of lack of stress resilience, is prolonged escape latency compared to non-stressed rats and is labeled learned helplessness (LH). The other behavior suggestive of stress resilience is normal escape latency and is labeled non-helpless (NH). This study examines the effects of unpredictable, inescapable tail-shock stress (TSS) on alpha(2)-adrenoceptor (alpha(2A)-AR) and corticotropin-releasing factor 1 receptor (CRF1-R) regulation as well as protein levels of G protein-coupled receptor kinase 3 (GRK3), GRK2, tyrosine hydroxylase (TH) plus carbonylated protein levels in locus coeruleus (LC), amygdala (AMG), cortex (COR) and striatum (SIR). In NH rats, alpha(2A)-AR and CRF1-R were significantly down-regulated in LC after TSS. No changes in these receptor levels were observed in the LC of LH rats. GRK3, which phosphorylates receptors and thereby contributes to alpha(2A)-AR and CRF1-R down-regulation, was reduced in the LC of LH but not NH rats. GRK2 levels were unchanged. In AMG, GRK3 but not GRK2 levels were reduced in LH but not NH rats, and receptor regulation was impaired in LH rats. In STR, no changes in GRK3 or GRK2 levels were observed. Finally, protein carbonylation, an index of oxidative stress, was increased in the LC and AMG of LH but not NH rats. We suggest that reduced stress resilience after TSS may be related to oxidative stress, depletion of GRK3 and impaired regulation of alpha(2A)-AR and CRF1-R in LC.

• 出版日期2011-8-1