Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that intracerebroventricular administration of NPY reduces the expression of social fear via simultaneous activation of Y1 and Y2 receptors in a mouse model of social fear conditioning (SFC). In the present study, we investigated whether the anteroventral bed nucleus of the stria terminalis (BNSTav) mediates these effects of NPY, given the important role of BNSTav in regulating anxiety- and fear-related behaviors. We show that while NPY (0.1 nmol/0.2 μl/side) did not reduce the expression of SFC-induced social fear in male CD1 mice, it reduced the expression of both cued and contextual fear by acting on Y2 but not on Y1 receptors within the BNSTav. Prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 μl/side) but not of the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 μl/side) blocked the effects of NPY on the expression of cued and contextual fear. Similarly, NPY exerted non-social anxiolytic-like effects in the elevated plus maze test but not social anxiolytic-like effects in the social approach avoidance test by acting on Y2 receptors and not on Y1 receptors within the BNSTav. These results suggest that administration of NPY within the BNSTav exerts robust Y2 receptor-mediated fear-reducing and anxiolytic-like effects specifically in non-social contexts and add a novel piece of evidence regarding the neural underpinnings underlying the effects of NPY on conditioned fear and anxiety-like behavior.

神经肽 Y (NPY) 具有类似抗焦虑的作用，有助于消除啮齿类动物的暗示恐惧和情境恐惧。我们之前已经证明，在社交恐惧调节（SFC）小鼠模型中，脑室内注射 NPY 可通过同时激活 Y1 和 Y2 受体来减少社交恐惧的表达。在本研究中，鉴于 BNSTav 在调节焦虑和恐惧相关行为中的重要作用，我们研究了终纹前腹床核 (BNSTav) 是否介导 NPY 的这些作用。我们发现，虽然 NPY（0.1 nmol/0.2 μl/侧）并没有减少雄性 CD1 小鼠中 SFC 诱导的社交恐惧的表达，但它通过作用于 Y2 受体而不是作用于 Y1 受体，减少了提示恐惧和情境恐惧的表达。 BNSTav。预先给予Y2受体拮抗剂BIIE0246（0.2nmol/0.2μl/侧）而非Y1受体拮抗剂BIBO3304三氟乙酸盐（0.2nmol/0.2μl/侧）可阻断NPY对暗示和情境恐惧表达的影响。类似地，NPY 在高架十字迷宫测试中发挥非社交抗焦虑样作用，但在社交接近回避测试中通过作用于 BNSTav 内的 Y2 受体而不是 Y1 受体而发挥非社交抗焦虑样作用。这些结果表明，在 BNSTav 内施用 NPY 可发挥强大的 Y2 受体介导的恐惧减少和抗焦虑样作用，特别是在非社交环境中，并为 NPY 对条件性恐惧和条件性恐惧的影响的神经基础提供了新的证据。类似焦虑的行为。