Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience.
Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience.
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DOI：
10.3390/brainsci12070860
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发表时间：
2022-06-29
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
--
作者：
蓝斑去甲肾上腺素能核是大脑应激回路的关键组成部分。在应激过程中，神经肽促肾上腺皮质激素释放因子（CRF）分泌到LC上，增加LC输出和大脑中去甲肾上腺素浓度，这被认为是促进焦虑样行为。LC也受几种结构的神经支配，这些结构在应激终止时合成并释放内源性阿片肽脑啡肽到LC上。虽然LC中CRF神经传递在介导焦虑样行为和应激行为反应中的作用已得到很好的表征，但LC表达的δ-阿片受体的脑啡肽能信号传导的作用相对研究不足。我们以前已经表明，急性应激暴露增加LC活动和焦虑样行为至少一周。在这里，我们扩展这些发现表明，这些影响可能介导的至少部分通过应激诱导的下调DORs内LC。此外，DORs在LC中的过表达阻断了应激对LC放电特性和焦虑样行为的影响。此外，脑啡肽的LC内输注阻断应激诱导的冻结行为，促进条件性位置偏爱。这些发现表明，在LC内DORs的脑啡肽能神经传递是应激行为反应的重要组成部分，也可能驱动奖励相关行为。
The noradrenergic nucleus locus coeruleus is a key component of the stress circuitry of the brain. During stress, the neuropeptide corticotropin-releasing factor (CRF) is secreted onto LC, increasing LC output and norepinephrine concentration in the brain, which is thought to promote anxiety-like behavior. LC is also innervated by several structures that synthesize and release the endogenous opioid peptide enkephalin onto LC upon stressor termination. While the role of CRF neurotransmission within LC in mediating anxiety-like behavior and the behavioral response to stress has been well characterized, the role of enkephalinergic signaling at LC-expressed δ-opioid receptors has been comparatively understudied. We have previously shown that acute stressor exposure increases LC activity and anxiety-like behavior for at least one week. Here, we extend these findings by showing that these effects may be mediated at least in part through stress-induced downregulation of DORs within LC. Furthermore, overexpression of DORs in LC blocks the effects of stress on both LC firing properties and anxiety-like behavior. In addition, intra-LC infusions of enkephalin blocked stress-induced freezing behavior and promoted conditioned place preference. These findings indicate that enkephalinergic neurotransmission at DORs within LC is an important component of the behavioral response to stress and may drive reward-related behavior as well.
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DOI：
10.1038/s41583-020-0360-9
发表时间：
2020-11
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Poe GR;Foote S;Eschenko O;Johansen JP;Bouret S;Aston-Jones G;Harley CW;Manahan-Vaughan D;Weinshenker D;Valentino R;Berridge C;Chandler DJ;Waterhouse B;Sara SJ
通讯作者：
Sara SJ
影响因子：
16.2
作者：
McCall JG;Al-Hasani R;Siuda ER;Hong DY;Norris AJ;Ford CP;Bruchas MR
通讯作者：
Bruchas MR
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。
影响因子：
4.7
作者：
Curtis AL;Leiser SC;Snyder K;Valentino RJ
通讯作者：
Valentino RJ
DOI：
10.1073/pnas.86.19.7321
发表时间：
1989-10-01
影响因子：
11.1
作者：
COSTA, T;HERZ, A
通讯作者：
HERZ, A
影响因子：
7.6
作者：
Morena, Maria;Berardi, Andrea;Campolongo, Patrizia
通讯作者：
Campolongo, Patrizia