Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Int J Mol Sci. 2021 Sep 20;22(18):10142. doi: 10.3390/ijms221810142.
Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We previously showed that intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC) and localized these effects to the dorsolateral septum (DLS) and central amygdala (CeA). In the present study, we aimed to identify the receptor subtypes that mediate these local effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduced the expression of SFC-induced social fear in a brain region- and receptor-specific manner in male mice. In the DLS, NPY reduced the expression of social fear by acting on Y2 receptors but not on Y1 receptors. As such, prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 μL/side) but not the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 μL/side) blocked the effects of NPY in the DLS. In the CeA, however, BIBO3304 trifluoroacetate but not BIIE0246 blocked the effects of NPY, suggesting that NPY reduced the expression of social fear by acting on Y1 receptors but not Y2 receptors within the CeA. This study suggests that at least two distinct receptor subtypes are differentially recruited in the DLS and CeA to mediate the effects of NPY on the expression of social fear.
神经肽 Y（NPY）具有抗焦虑样作用，并促进啮齿动物条件性恐惧的消退。我们之前的研究表明，脑室注射 NPY 可减少社交恐惧条件反射（SFC）小鼠模型中社会恐惧的表达，并将这些作用定位于侧脑室隔（DLS）和中央杏仁核（CeA）。在本研究中，我们旨在确定介导 NPY 局部作用的受体亚型。我们发现，NPY（0.1 nmol/0.2 μL/侧）以脑区和受体特异性的方式减少了雄性小鼠 SFC 诱导的社会恐惧的表达。在 DLS 中，NPY 通过作用于 Y2 受体而不是 Y1 受体来减少社会恐惧的表达。因此，预先给予 Y2 受体拮抗剂 BIIE0246（0.2 nmol/0.2 μL/侧）而非 Y1 受体拮抗剂 BIBO3304 三氟乙酸（0.2 nmol/0.2 μL/侧）可阻断 DLS 中 NPY 的作用。然而，在 CeA 中，BIBO3304 三氟乙酸而非 BIIE0246 阻断了 NPY 的作用，表明 NPY 通过作用于 CeA 中的 Y1 受体而不是 Y2 受体来减少社会恐惧的表达。这项研究表明，至少两种不同的受体亚型在 DLS 和 CeA 中被差异招募，以介导 NPY 对社会恐惧表达的影响。
