Corticotropin releasing factor (CRF) is a neuropeptide widely distributed in the brain as a hormonal modulator and neurotransmitter. The best known behavioral function of CRF is activation of stress and anxiety via the hypothalamus and limbic structures but the role of CRF in the cortex is still poorly understood. Our previous studies have shown anxiolytic-like effects of high doses of CRF injected into the Fr2 frontal cortex and involvement of CRF1 receptors (R) in that effect. These results seemed to be controversial as most other studies suggested anxiogenic and not anxiolytic effects of CRF1R stimulation. Since stress is associated with adrenergic system, in the present study, we focused on participation of alpha1 and alpha2 or beta adrenergic receptors in the anxiolytic-like effect of CRF. Moreover, we verified whether these effects of CRF in the Fr2 were really connected with CRF1R.

Male Wistar rats were bilaterally microinjected with CRF in a dose of 0.2 μg/1 μl/site or with the specific agonist of CRF1R, stressin 1 (0.2–0.0125 μg/1 μl/site) into the Fr2 area. The elevated plus maze (EPM) test was performed 30 min later to assess the anxiolysis. An involvement of noradrenergic receptors in the CRF induced anxiolytic-like effect in the Fr2 was studied by pretreatment with the alpha1 antagonist prazosin, alpha2 agonist clonidine, alpha2 antagonist RS 79948 or beta antagonist propranolol, 20–30 min before CRF. The influence on anxiety was assessed in the EPM test. The results show that anxiolytic behavior after CRF microinjection into the Fr2 area seems to be mainly connected with the CRF1R activation because a similar effect was observed after stressin 1 administration and it was blocked by CRF1R antagonist. The results observed after administration of noradrenergic ligands indicated that anxiolytic effects of CRF in the Fr2 engaged the alpha1 and alpha2 adrenergic receptors but not beta receptors.

促肾上腺皮质激素释放因子 (CRF) 是一种广泛分布于大脑中的神经肽，作为​​激素调节剂和神经递质。CRF 最著名的行为功能是通过下丘脑和边缘结构激活压力和焦虑，但 CRF 在皮质中的作用仍然知之甚少。我们之前的研究表明，将高剂量 CRF 注射到 Fr2 额叶皮层会产生类似抗焦虑的作用，并且 CRF1 受体 (R) 参与了这种作用。这些结果似乎是有争议的，因为大多数其他研究表明 CRF1R 刺激产生焦虑而不是抗焦虑作用。由于压力与肾上腺素能系统有关，因此在本研究中，我们重点关注 α1 和 α2 或β 肾上腺素能受体参与 CRF 的抗焦虑样作用。而且，

雄性 Wistar 大鼠双侧显微注射 CRF，剂量为 0.2 μg/1 μl/位点，或 CRF1R 的特异性激动剂应力素 1（0.2–0.0125 μg/1 μl/位点）注射到 Fr2 区域。30 分钟后进行高架十字迷宫 (EPM) 测试以评估抗焦虑。通过在 CRF 前 20-30 分钟用 α1 拮抗剂哌唑嗪、α2 激动剂可乐定、α2 拮抗剂 RS 79948 或β 拮抗剂普萘洛尔预处理，研究了去甲肾上腺素能受体参与 CRF 诱导的 Fr2 抗焦虑样作用。在 EPM 测试中评估了对焦虑的影响。结果表明，CRF 显微注射到 Fr2 区域后的抗焦虑行为似乎主要与 CRF1R 激活有关，因为在 Stressin 1 给药后观察到类似的效果，并且它被 CRF1R 拮抗剂阻断。