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

Authors Khedr L, Nassar N, El-Denshary EE, Abdel-tawab A

Received 21 April 2015

Accepted for publication 11 June 2015

Published 13 November 2015 Volume 2015:11 Pages 2887—2901

DOI https://doi.org/10.2147/NDT.S87089

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Miao Sun

Peer reviewer comments 4

Editor who approved publication: Dr Roger Pinder


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

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