Restraint Stress Alters Nociceptin/Orphanin FQ and CRF Systems in the Rat Central Amygdala: Significance for Anxiety-Like Behaviors
Restraint Stress Alters Nociceptin/Orphanin FQ and CRF Systems in the Rat Central Amygdala: Significance for Anxiety-Like Behaviors
复制标题
DOI：
10.1523/jneurosci.2400-13.2014
复制
发表时间：
2014-01-08
影响因子：
5.3
通讯作者：
Roberto, Marisa
中科院分区：
文献类型：
--
作者：
Ciccocioppo, Roberto;de Guglielmo, Giordano;Roberto, Marisa
促肾上腺皮质激素释放因子（CRF）是应激反应的主要调节因子，而痛觉啡肽/孤啡肽FQ （N/OFQ）在这些应激反应的调节中起着重要作用。因此，在这项多学科研究中，我们探讨了N/OFQ和CRF系统在应激反应中的关系。利用原位杂交技术（ISH），我们评估了身体约束应激对杏仁核不同分支中CRF和N/ ofq相关基因表达的影响，杏仁核是调节应激反应和焦虑样行为的关键大脑结构。我们发现，在身体约束后，CeA和BLA中NOP选择性上调，CRF1受体转录本下调。因此，我们在杏仁核中央核（CeA）进行了gabaa介导的ipsp的细胞内电生理记录，以探索该脑区域CRF和N/OFQ系统之间的功能相互作用。急性应用CRF显著增加CeA的ipsp，而这种增强被N/OFQ阻断。重要的是，与不受约束的大鼠相比，应激抑制大鼠的基线CeA - gaba能反应升高，N/OFQ对ipsp的抑制作用更大。NOP拮抗剂[Nphe1]-nociceptin(1-13) NH2增加了约束大鼠的IPSP振幅，而在非约束大鼠中没有，提示急性应激后N/OFQ系统的功能性募集。最后，我们评估了N/OFQ微注射到CeA后，约束应激大鼠和非约束应激大鼠的焦虑样反应。cea内注射N/OFQ可显著、选择性地减少高加迷宫中约束大鼠的焦虑样行为。这些综合结果表明，急性应激增加了CeA中的N/OFQ系统，并且N/OFQ具有抗应激特性。
Corticotropin releasing factor (CRF) is the primary mediator of stress responses, and nociceptin/orphanin FQ (N/OFQ) plays an important role in the modulation of these stress responses. Thus, in this multidisciplinary study, we explored the relationship between the N/OFQ and the CRF systems in response to stress. Using in situ hybridization (ISH), we assessed the effect of body restraint stress on the gene expression of CRF and N/OFQ-related genes in various subdivisions of the amygdala, a critical brain structure involved in the modulation of stress response and anxiety-like behaviors. We found a selective upregulation of the NOP and downregulation of the CRF1 receptor transcripts in the CeA and in the BLA after body restraint. Thus, we performed intracellular electrophysiological recordings of GABAA-mediated IPSPs in the central nucleus of the amygdala (CeA) to explore functional interactions between CRF and N/OFQ systems in this brain region. Acute application of CRF significantly increased IPSPs in the CeA, and this enhancement was blocked by N/OFQ. Importantly, in stress-restraint rats, baseline CeA GABAergic responses were elevated and N/OFQ exerted a larger inhibition of IPSPs compared with unrestraint rats. The NOP antagonist [Nphe1]-nociceptin(1-13) NH2 increased the IPSP amplitudes in restraint rats but not in unrestraint rats, suggesting a functional recruitment of the N/OFQ system after acute stress. Finally, we evaluated the anxiety-like response in rats subjected to restraint stress and nonrestraint rats after N/OFQ microinjection into the CeA. Intra-CeA injections of N/OFQ significantly and selectively reduced anxiety-like behavior in restraint rats in the elevated plus maze. These combined results demonstrate that acute stress increases N/OFQ systems in the CeA and that N/OFQ has antistress properties.