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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Dove Medical Press
2015
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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) |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
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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 |
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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 |
work_keys_str_mv |
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