κ Opioid Receptor-Dynorphin Signaling in the Central Amygdala Regulates Conditioned Threat Discrimination and Anxiety. 2021

Madison A Baird, and TingTing Y Hsu, and Rachel Wang, and Barbara Juarez, and Larry S Zweifel
Department of Pharmacology, University of Washington, Seattle, WA 98115.

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, Oprk1, 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, Pdyn, in the CeA has no effect on anxiety or conditioned threat discrimination. However, inactivation of Pdyn from multiple sources, intrinsic and extrinsic to the CeA phenocopies Oprk1 inactivation. These findings suggest that dynorphin inputs to the CeA signal through KOR to promote threat discrimination and dampen anxiety.

UI MeSH Term Description Entries
D004399 Dynorphins A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters. Dynorphin,Dynorphin (1-17),Dynorphin A,Dynorphin A (1-17)
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001007 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS. Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017473 Receptors, Opioid, kappa A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins. Opioid Receptors, kappa,Receptors, kappa,Receptors, kappa Opioid,kappa Receptors,kappa Opioid Receptor,kappa Receptor,Opioid Receptor, kappa,Receptor, kappa,Receptor, kappa Opioid,kappa Opioid Receptors
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D066274 Central Amygdaloid Nucleus A nucleus located in the caudal half of the amygdala. It is a primary region involved in controlling responses and receives many intrinsic GABAergic amygdaloid connections. Central Amygdala Nucleus,Central Amygdala,Central Nucleus of Amygdala,Central Nucleus of the Amygdala,Amygdala Central Nucleus,Amygdala Nucleus, Central,Amygdala, Central,Amygdalas, Central,Amygdaloid Nucleus, Central,Central Amygdalas,Nucleus, Central Amygdala,Nucleus, Central Amygdaloid

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