Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cair...

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Autores principales: Khedr LH, Nassar NN, El-Denshary ES, Abdel-tawab AM
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:160d54eab0024e32be44f7c1464fd3522021-12-02T08:36:07ZParoxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats1178-2021https://doaj.org/article/160d54eab0024e32be44f7c1464fd3522015-11-01T00:00:00Zhttps://www.dovepress.com/paroxetine-ameliorates-changes-in-hippocampal-energy-metabolism-in-chr-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS) model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX) in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally). Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT) was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c), caspase-3 (Casp-3), as well as nitric oxide metabolites (NOx) were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001) as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001). Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3Khedr LHNassar NNEl-Denshary ESAbdel-tawab AMDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2015, Iss default, Pp 2887-2901 (2015)
institution DOAJ
collection DOAJ
language EN
topic Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Khedr LH
Nassar NN
El-Denshary ES
Abdel-tawab AM
Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats
description Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS) model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX) in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally). Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT) was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c), caspase-3 (Casp-3), as well as nitric oxide metabolites (NOx) were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001) as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001). Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3
format article
author Khedr LH
Nassar NN
El-Denshary ES
Abdel-tawab AM
author_facet Khedr LH
Nassar NN
El-Denshary ES
Abdel-tawab AM
author_sort Khedr LH
title Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats
title_short Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats
title_full Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats
title_fullStr Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats
title_full_unstemmed Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats
title_sort paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/160d54eab0024e32be44f7c1464fd352
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