Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression

Depression has been linked to the dysfunction of the autonomic nervous system, which may cause dysregulation of the cardiovascular system. One promising therapeutic strategy for treating different diseases is inhibiting the enzyme fatty acid amide hydrolase (FAAH), which increases the availability o...

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Main Authors: Ferizović Harisa, Spasojević Nataša, Janković Milica, Stefanović Bojana, Dronjak Slađana
Format: Article
Language:English
Published: University of Belgrade, University of Novi Sad 2024-01-01
Series:Archives of Biological Sciences
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Online Access:https://doiserbia.nb.rs/img/doi/0354-4664/2024/0354-46642400028F.pdf
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author Ferizović Harisa
Spasojević Nataša
Janković Milica
Stefanović Bojana
Dronjak Slađana
author_facet Ferizović Harisa
Spasojević Nataša
Janković Milica
Stefanović Bojana
Dronjak Slađana
author_sort Ferizović Harisa
collection DOAJ
description Depression has been linked to the dysfunction of the autonomic nervous system, which may cause dysregulation of the cardiovascular system. One promising therapeutic strategy for treating different diseases is inhibiting the enzyme fatty acid amide hydrolase (FAAH), which increases the availability of endogenous cannabinoids. We examined the effect of chronic FAAH inhibition with URB597 treatment on the noradrenaline (NA) content, synthesis, transport, and degradation in the left ventricle of female and male rats exposed to chronic unpredictable stress (CUS). CUS decreased the levels of both NA and dopamine-β-hydroxylase (DBH) protein in male rats and decreased NA transporter (NET) protein levels in female rats while elevating monoamine oxidase A (MAO-A) in both sexes. Intraperitoneal URB597 application led to increased expression of DBH in stressed males, as well as elevated NET protein levels and decreased MAO-A protein levels in the left ventricle of stressed rats of both sexes. URB597 treatment may have a beneficial effect on the cardiovascular system in an animal model of depression with heightened sympathoneural activity.
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language English
publishDate 2024-01-01
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spelling doaj-art-5f567c9512b14cf6b256f61806584f302025-01-30T06:38:34ZengUniversity of Belgrade, University of Novi SadArchives of Biological Sciences0354-46641821-43392024-01-0176335936710.2298/ABS240731028F0354-46642400028FRegulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depressionFerizović Harisa0https://orcid.org/0000-0001-5667-7254Spasojević Nataša1https://orcid.org/0000-0001-8843-7976Janković Milica2https://orcid.org/0000-0001-5189-9472Stefanović Bojana3https://orcid.org/0000-0002-1360-5514Dronjak Slađana4https://orcid.org/0000-0002-4334-8002Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences “Vinča”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology and Endocrinology, Institute of Nuclear Sciences “Vinča”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology and Endocrinology, Institute of Nuclear Sciences “Vinča”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology and Endocrinology, Institute of Nuclear Sciences “Vinča”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Biology and Endocrinology, Institute of Nuclear Sciences “Vinča”, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepression has been linked to the dysfunction of the autonomic nervous system, which may cause dysregulation of the cardiovascular system. One promising therapeutic strategy for treating different diseases is inhibiting the enzyme fatty acid amide hydrolase (FAAH), which increases the availability of endogenous cannabinoids. We examined the effect of chronic FAAH inhibition with URB597 treatment on the noradrenaline (NA) content, synthesis, transport, and degradation in the left ventricle of female and male rats exposed to chronic unpredictable stress (CUS). CUS decreased the levels of both NA and dopamine-β-hydroxylase (DBH) protein in male rats and decreased NA transporter (NET) protein levels in female rats while elevating monoamine oxidase A (MAO-A) in both sexes. Intraperitoneal URB597 application led to increased expression of DBH in stressed males, as well as elevated NET protein levels and decreased MAO-A protein levels in the left ventricle of stressed rats of both sexes. URB597 treatment may have a beneficial effect on the cardiovascular system in an animal model of depression with heightened sympathoneural activity.https://doiserbia.nb.rs/img/doi/0354-4664/2024/0354-46642400028F.pdfnoradrenalineleft ventriclechronic unpredictable stressendocannabinoidsexperimental rat
spellingShingle Ferizović Harisa
Spasojević Nataša
Janković Milica
Stefanović Bojana
Dronjak Slađana
Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression
Archives of Biological Sciences
noradrenaline
left ventricle
chronic unpredictable stress
endocannabinoids
experimental rat
title Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression
title_full Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression
title_fullStr Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression
title_full_unstemmed Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression
title_short Regulation of noradrenaline synthesis, uptake, and degradation in the left ventricle by fatty acid amide hydrolase (FAAH) inhibitor URB597 in the chronic unpredictable stress model of depression
title_sort regulation of noradrenaline synthesis uptake and degradation in the left ventricle by fatty acid amide hydrolase faah inhibitor urb597 in the chronic unpredictable stress model of depression
topic noradrenaline
left ventricle
chronic unpredictable stress
endocannabinoids
experimental rat
url https://doiserbia.nb.rs/img/doi/0354-4664/2024/0354-46642400028F.pdf
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