Differential effects of inescapable stress on locus coeruleus GRK3, alpha2-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: a potential link to stress resilience.

Differential effects of inescapable stress on locus coeruleus GRK3, alpha2-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: a potential link to stress resilience.
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DOI:
10.1016/j.bbr.2011.02.018
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发表时间:
2011-08-01
影响因子:
2.7
通讯作者:
Eikenburg, Douglas C.
Eikenburg, Douglas C.
中科院分区:
心理学3区
文献类型:
--
作者:
Taneja, Manish;Salim, Samina;Saha, Kaustuv;Happe, H. Kevin;Qutna, Nidal;Petty, Frederick;Bylund, David B.;Eikenburg, Douglas C.

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大鼠暴露于不可预测的,不可避免的压力导致两个不同的行为在随后的逃避测试。一个行为,暗示缺乏压力弹性,是延长逃避潜伏期相比,非应激大鼠,并标记为习得性无助(LH)。另一个暗示压力恢复力的行为是正常的逃避潜伏期,被标记为非无助(NH)。本研究探讨了不可预测的、不可避免的尾部休克应激(TSS)对蓝斑(LC)、杏仁核(AMG)、皮质(COR)和纹状体(STR)α 2-肾上腺素受体(α2-AR)和促肾上腺皮质激素释放因子1受体(CRF 1)的调节以及G蛋白偶联受体激酶3(GRK 3)、GRK 2、酪氨酸羟化酶(TH)和羰基化蛋白水平的影响。在NH大鼠,TSS后LC中α2-AR和CRF 1受体显著下调。在LH大鼠的LC中未观察到这些受体水平的变化。GRK 3使受体磷酸化,从而导致α2-AR和CRF 1受体下调,在LH而不是NH大鼠的LC中减少。GRK 2水平没有变化。在AMG中,GRK 3而非GRK 2水平在LH而非NH大鼠中降低,并且受体调节在LH大鼠中受损。在STR中,未观察到GRK 3或GRK 2水平的变化。最后,蛋白质羰基化,氧化应激的指标,增加了在LC和AMG的LH,但NH大鼠。我们认为TSS后应激恢复能力降低可能与LC中氧化应激、GRK 3耗竭以及α2-AR和CRF 1受体调节受损有关。
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 alpha2-adrenoceptor (α2-AR) and corticotropin-releasing factor 1 receptor (CRF1) 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 (STR). In NH rats, α2-AR and CRF1 receptors 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 α2-AR and CRF1 receptor 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 α2-AR and CRF1 receptor in LC.
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发表时间: 2007-01-15
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DOI: 10.1016/s0006-8993(01)03046-3
发表时间: 2001-11-01
期刊: MOLECULAR BRAIN RESEARCH
影响因子: --
作者:
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