Baird Madison A, Hsu TingTing Y, Wang Rachel, Juarez Barbara, Zweifel Larry S
Department of Pharmacology, University of Washington, Seattle, WA 98115.
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98115.
eNeuro. 2021 Feb 4;8(1). doi: 10.1523/ENEURO.0370-20.2020. Print 2021 Jan-Feb.
Neuropeptides within the central nucleus of the amygdala (CeA) potently modulate neuronal excitability and have been shown to regulate conditioned threat discrimination and anxiety. Here, we investigated the role of κ opioid receptor (KOR) and its endogenous ligand dynorphin in the CeA for regulation of conditioned threat discrimination and anxiety-like behavior in mice. We demonstrate that reduced KOR expression through genetic inactivation of the KOR encoding gene, , in the CeA results in increased anxiety-like behavior and impaired conditioned threat discrimination. In contrast, reduction of dynorphin through genetic inactivation of the dynorphin encoding gene, , in the CeA has no effect on anxiety or conditioned threat discrimination. However, inactivation of from multiple sources, intrinsic and extrinsic to the CeA phenocopies inactivation. These findings suggest that dynorphin inputs to the CeA signal through KOR to promote threat discrimination and dampen anxiety.
杏仁核中央核（CeA）内的神经肽可有效调节神经元兴奋性，并已被证明可调节条件性威胁辨别和焦虑。在此，我们研究了κ阿片受体（KOR）及其内源性配体强啡肽在CeA中对小鼠条件性威胁辨别和焦虑样行为调节的作用。我们证明，通过在CeA中对编码KOR的基因进行基因失活来降低KOR表达，会导致焦虑样行为增加和条件性威胁辨别受损。相比之下，通过在CeA中对编码强啡肽的基因进行基因失活来减少强啡肽，对焦虑或条件性威胁辨别没有影响。然而，来自CeA内在和外在多种来源的失活模拟了失活。这些发现表明，强啡肽向CeA的输入通过KOR发出信号，以促进威胁辨别并减轻焦虑。
