1 型促肾上腺皮质素释放因子受体在调节幼年和成年大鼠伏隔核神经递质水平方面存在差异。
Type 1 Corticotropin-Releasing Factor Receptor Differentially Modulates Neurotransmitter Levels in the Nucleus Accumbens of Juvenile versus Adult Rats.
机构信息
Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, Santiago 8331150, Chile.
出版信息
Int J Mol Sci. 2022 Sep 16;23(18):10800. doi: 10.3390/ijms231810800.
Adversity is particularly pernicious in early life, increasing the likelihood of developing psychiatric disorders in adulthood. Juvenile and adult rats exposed to social isolation show differences in anxiety-like behaviors and significant changes in dopamine (DA) neurotransmission in the nucleus accumbens (NAc). Brain response to stress is partly mediated by the corticotropin-releasing factor (CRF) system, composed of CRF and its two main receptors, CRF-R1 and CRF-R2. In the NAc shell of adult rats, CRF induces anxiety-like behavior and changes local DA balance. However, the role of CRF receptors in the control of neurotransmission in the NAc is not fully understood, nor is it known whether there are differences between life stages. Our previous data showed that infusion of a CRF-R1 antagonist into the NAc of juvenile rats increased DA levels in response to a depolarizing stimulus and decreased basal glutamate levels. To extend this analysis, we now evaluated the effect of a CRF-R1 antagonist infusion in the NAc of adult rats. Here, we describe that the opposite occurred in the NAc of adult compared to juvenile rats. Infusion of a CRF-R1 antagonist decreased DA and increased glutamate levels in response to a depolarizing stimulus. Furthermore, basal levels of DA, glutamate, and γ-Aminobutyric acid (GABA) were similar in juvenile animals compared to adults. CRF-R1 protein levels and localization were not different in juvenile compared to adult rats. Interestingly, we observed differences in the signaling pathways of CRF-R1 in the NAc of juveniles compared to adult rats. We propose that the function of CRF-R1 receptors is differentially modulated in the NAc according to life stage.
逆境在生命早期尤为有害,增加了成年后患精神障碍的可能性。暴露于社会隔离的幼年和成年大鼠表现出类似焦虑的行为差异,以及伏隔核(NAc)中多巴胺(DA)神经传递的显著变化。大脑对应激的反应部分由促肾上腺皮质释放因子(CRF)系统介导,该系统由 CRF 及其两个主要受体 CRF-R1 和 CRF-R2 组成。在成年大鼠的 NAc 壳中,CRF 诱导类似焦虑的行为并改变局部 DA 平衡。然而,CRF 受体在 NAc 中控制神经传递的作用尚未完全阐明,也不知道在生命阶段之间是否存在差异。我们之前的数据表明,在幼年大鼠的 NAc 中输注 CRF-R1 拮抗剂会增加对去极化刺激的 DA 水平,并降低基础谷氨酸水平。为了扩展此分析,我们现在评估了在成年大鼠的 NAc 中输注 CRF-R1 拮抗剂的效果。在这里,我们描述了与幼年大鼠相比,成年大鼠 NAc 中发生了相反的情况。CRF-R1 拮抗剂的输注会降低去极化刺激时的 DA 并增加谷氨酸水平。此外,与成年动物相比,幼年动物的 NAc 中的 DA、谷氨酸和γ-氨基丁酸(GABA)的基础水平相似。CRF-R1 蛋白水平和定位在幼年大鼠与成年大鼠之间没有差异。有趣的是,我们在幼年和成年大鼠的 NAc 中观察到 CRF-R1 信号通路的差异。我们提出,CRF-R1 受体在 NAc 中的功能根据生命阶段而不同调节。