Oxytocin Stimulates Extracellular Ca2+ Influx Through TRPV2 Channels in Hypothalamic Neurons to Exert Its Anxiolytic Effects

van den Burg, Erwin H. and Stindl, Julia and Grund, Thomas and Neumann, Inga D. and Strauss, Olaf (2015) Oxytocin Stimulates Extracellular Ca2+ Influx Through TRPV2 Channels in Hypothalamic Neurons to Exert Its Anxiolytic Effects. NEUROPSYCHOPHARMACOLOGY, 40 (13). pp. 2938-2947. ISSN 0893-133X, 1740-634X

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Abstract

There is growing interest in anxiolytic and pro-social effects of the neuropeptide oxytocin (OXT), but the underlying intraneuronal mechanisms are largely unknown. Here we examined OXT-mediated anxiolysis in the hypothalamic paraventricular nucleus (PVN) of rats and effects of OXT administration on signaling events in hypothalamic primary and immortalized cells. In vivo, the application of SKF96365 prevented the anxiolytic activity of OXT in the PVN, suggesting that changes in intracellular Ca2+ mediate the acute OXT behavioral effects. In vitro, mainly in the neurons with autonomous Ca2+ oscillations, OXT increased intracellular Ca2+ concentration and oscillation amplitude. Pharmacological intervention revealed OXT-dependent changes in Ca2+ signaling that required activation of transient receptor potential vanilloid type-2 channel (TRPV2), mediated by phosphoinositide 3-kinase. TRPV2 induced the activation of the anxiolytic mitogen-activated protein kinase kinase (MEK1/2). In situ, immunohistochemistry revealed co-localization of TRPV2 and OXT in the PVN. Thus, functional and pharmacological analyses identified TRPV2 as a mediator of anxiolytic effects of OXT, conveying the OXT signal to MEK1/2 via modulation of intracellular Ca2+.

Item Type: Article
Uncontrolled Keywords: RECEPTOR POTENTIAL CHANNELS; ANXIETY-RELATED BEHAVIOR; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; VASOPRESSIN; FEAR; ACTIVATION; EXPRESSION; RELEASE; SYSTEM;
Subjects: 500 Science > 590 Zoological sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Augenheilkunde
Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 May 2019 07:49
Last Modified: 06 May 2019 07:49
URI: https://pred.uni-regensburg.de/id/eprint/4426

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