Predator stress engages corticotropin-releasing factor and opioid systems to alter the operating mode of locus coeruleus norepinephrine neurons.
Predator stress engages corticotropin-releasing factor and opioid systems to alter the operating mode of locus coeruleus norepinephrine neurons.
复制标题
捕食者应激会利用促肾上腺皮质激素释放因子和阿片类药物系统来改变蓝斑去甲肾上腺素神经元的工作模式。
DOI：
10.1016/j.neuropharm.2011.11.020
复制
发表时间：
2012-03
影响因子：
4.7
通讯作者：
Valentino RJ
中科院分区：
文献类型：
--
作者：
Curtis AL;Leiser SC;Snyder K;Valentino RJ
去甲肾上腺素核团蓝斑(LC)参与了应激反应的认知方面，部分是通过应激相关神经肽促肾上腺皮质激素释放因子(CRF)的调节。LC神经元以紧张和时相模式放电，这两种模式不同地调节注意力和行为。在这里，暴露于与行为学相关的应激源，捕食者气味，对未麻醉大鼠的自发(强直)和听觉诱发(相)LC放电的影响进行了表征。与慢性肾功能衰竭的效应相似，应激源呈现增加了紧张性LC放电，减少了时相听觉诱发放电，从而降低了感觉反应的信噪比。这种应激诱导的LC放电向高紧张性模式的转变可被CRF拮抗剂阻止。此外，应激期间CRF拮抗揭示了由阿片类药物介导的紧张性放电速率的大幅下降，因为这是由阿片受体拮抗剂纳洛酮预先阻止的。使用拮抗剂组合消除CRF和阿片类药物的影响，使LC活性不受应激源的影响。这些结果表明，在应激过程中，CRF和阿片类传入都参与了LC活动的微调。CRF的主要影响将LC活动的操作模式转变为高紧张性状态，这种状态被认为有助于行为灵活性，并可能在应对应激源时具有适应性。同时，压力产生了一种相反的类阿片影响，抑制了CRF的影响，并可能促进恢复到应激前的活动水平。CRF平衡的变化：LC的阿片类药物调节可能会导致应激脆弱性。
The norepinephrine nucleus, locus coeruleus (LC), has been implicated in cognitive aspects of the stress response, in part through its regulation by the stress-related neuropeptide, corticotropin-releasing factor (CRF). LC neurons discharge in tonic and phasic modes that differentially modulate attention and behavior. Here, the effects of exposure to an ethologically relevant stressor, predator odor, on spontaneous (tonic) and auditory-evoked (phasic) LC discharge were characterized in unanesthetized rats. Similar to the effects of CRF, stressor presentation increased tonic LC discharge and decreased phasic auditory-evoked discharge, thereby decreasing the signal-to-noise ratio of the sensory response. This stress-induced shift in LC discharge towards a high tonic mode was prevented by a CRF antagonist. Moreover, CRF antagonism during stress unmasked a large decrease in tonic discharge rate that was opioid mediated because it was prevented by pretreatment with the opiate antagonist, naloxone. Elimination of both CRF and opioid influences with an antagonist combination rendered LC activity unaffected by the stressor. These results demonstrate that both CRF and opioid afferents are engaged during stress to fine-tune LC activity. The predominant CRF influence shifts the operational mode of LC activity towards a high tonic state that is thought to facilitate behavioral flexibility and may be adaptive in coping with the stressor. Simultaneously, stress engages an opposing opioid influence that restrains the CRF influence and may facilitate recovery towards pre-stress levels of activity. Changes in the balance of CRF:opioid regulation of the LC could have consequences for stress vulnerability.