Neuroimaging data in humans and neurobiological studies in rodents have suggested an involvement of the insular cortex (IC) in anxiety manifestations. However, the local neurochemical mechanisms involved are still poorly understood. Corticotropin-releasing factor (CRF) neurotransmission has been described as a prominent neurochemical mechanism involved in the expression of anxiety-like behaviors, but the brain sites related are poorly understood. Additionally, several findings indicate that control of physiological and behavioral responses by the IC occurs in a site-specific manner along its rostrocaudal axis. Thus, this study is aimed at evaluating the effect of CRF receptor agonism and antagonism within the anterior and posterior subregions of the IC in controlling anxiety-related behaviors in the elevated plus maze (EPM). For this, independent groups (six groups) of animals received bilateral microinjections of vehicle, the selective CRF₁ receptor antagonist CP376395, or CRF into either the anterior or posterior subregions of the IC. Ten minutes later, the behavior in the EPM was evaluated for five minutes. Treatment of the anterior IC with CP376395, but not with CRF, increased the time and number of entries into the open arms of the EPM. CRF, but not the CRF₁ receptor antagonist, microinjected into the posterior IC also increased exploration of the EPM open arms. Taken together, these data indicate that CRFergic neurotransmission in the anterior IC is involved in the expression of anxiety-related behaviors in the EPM. This neurochemical mechanism does not seem to be activated within the posterior IC during exposure to the EPM, but the effects caused by CRF microinjection indicate that activation of CRF receptors in this IC subregion might evoke anxiolytic-like effects.

中文翻译：

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岛叶皮质前部和后部亚区域促肾上腺皮质激素释放因子受体的药理学操作不同地影响大鼠高架十字迷宫中的焦虑样行为

人类的神经影像数据和啮齿类动物的神经生物学研究表明，岛叶皮质（IC）与焦虑表现有关。然而，所涉及的局部神经化学机制仍然知之甚少。促肾上腺皮质激素释放因子（CRF）神经传递被描述为参与焦虑样行为表达的重要神经化学机制，但相关的大脑部位却知之甚少。此外，一些研究结果表明，IC 对生理和行为反应的控制是沿着其头尾轴以特定位点的方式发生的。因此，本研究旨在评估IC前部和后部亚区域内CRF受体激动和拮抗作用在控制高架十字迷宫（EPM）中焦虑相关行为的作用。为此，独立组（六组）的动物接受双侧显微注射载体、选择性 CRF ₁受体拮抗剂 CP376395 或 CRF 到 IC 的前部或后部亚区域。十分钟后，EPM 中的行为评估了五分钟。使用 CP376395（而非 CRF）治疗前 IC，增加了进入 EPM 张开臂的时间和次数。将 CRF（而非 CRF ₁受体拮抗剂）显微注射到后 IC 中也增加了对 EPM 张开臂的探索。总而言之，这些数据表明前 IC 中的 CRFergic 神经传递参与了 EPM 中焦虑相关行为的表达。在暴露于 EPM 期间，后 IC 内的这种神经化学机制似乎并未被激活，但 CRF 显微注射引起的效应表明，该 IC 亚区域中 CRF 受体的激活可能会引起抗焦虑样作用。