The translocator protein 18 kDa (TSPO) ligand etifoxine in an animal model of anxiety: Line- and sex-dependent effects on emotionality, stress reactivity, spine density, oxytocin receptors, steroids, and microbiome composition

URN to cite this document:

urn:nbn:de:bvb:355-epub-745799 Copy

DOI to cite this document:

10.5283/epub.74579 Copy

Fischer, Lilith ; Paschke, Bjarne ; Gareis, Franziska ; Schumacher, Michael ; Liere, Philippe ; Hiergeist, Andreas ; Gessner, André ; Rupprecht, Rainer ; Neumann, Inga D. ; Bosch, Oliver J.

License: Creative Commons Attribution Non-commercial No Derivatives 4.0 PDF - Published Version (6MB)

Date of publication of this fulltext: 08 Jan 2025 07:50

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Details

Item type:	Article
Open Access Type:	DEAL (Elsevier)
Journal or Publication Title:	Neuropharmacology
Publisher:	Elsevier
Volume:	266
Page Range:	p. 110282
Date:	24 December 2024
Institutions:	Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann)
Projects (Historical):	DFG FOR 2858, project number 422183249, DFG GRK2174, DFG 422179811
Identification Number:	Value Type 10.1016/j.neuropharm.2024.110282 DOI
Keywords:	Anxiety-related behavior, Corticosterone, Etifoxine, Passive stress-coping, Spine density, TSPO
Dewey Decimal Classification:	500 Science > 570 Life sciences 500 Science > 590 Zoological sciences
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Partially
Item ID:	74579

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Abstract

The treatment of stress-related disorders such as anxiety and depression is still challenging. One potential therapeutical option are neurosteroids. Their synthesis is promoted by ligands of the mitochondrial translocator protein 18 kDa (TSPO). We tested the TSPO ligand etifoxine (ETX) in a rat model of hyper-anxiety and depression-like behavior, i.e., in female and male HAB (high anxiety-related ...

Abstract

The treatment of stress-related disorders such as anxiety and depression is still challenging. One potential therapeutical option are neurosteroids. Their synthesis is promoted by ligands of the mitochondrial translocator protein 18 kDa (TSPO). We tested the TSPO ligand etifoxine (ETX) in a rat model of hyper-anxiety and depression-like behavior, i.e., in female and male HAB (high anxiety-related behavior) rats, as well as in respective low anxiety (LAB) and non-selected control (NAB) rats for behavioral, molecular, cellular, and physiological parameters. Daily acute i.p. treatment with ETX or vehicle over 5 or 9 days revealed that ETX was most effective in female HAB rats; it reduced anxiety levels (5 days) and OXT-R binding brain site-specifically (5 and 9 days), and increased spine density (5 days). The behavioral ETX effect exclusively found in female HABs was accompanied by increased 3β5α-THDOC levels, without any effect in female LABs and NABs and on other neurosteroids. In males of all breeding lines, ETX changed a total of 10 out of 23 brain steroids. Passive stress-coping during 10-min forced swimming was not affected by 9-day treatment with ETX, the resulting stress-induced plasma corticosterone levels were higher in ETX-treated NAB rats of both sexes compared with their VEH-treated groups. The fecal bacterial composition was similar but beta diversity differed between HABs and LABs and from NABs independent of sex; ETX treatment had no effect. Therefore, we propose considering the aspect of sex in treatment strategies for anxiety disorders. This is particularly important to establish better treatment regimens for women.

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Metadata last modified: 04 Sep 2025 15:49

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