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

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 adenos-ine 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

Acknowledgments

The authors greatly appreciate the efforts of Dr Hanan El Mohammady, Section Head, Serology, Disease Surveillance and Research Lab, US Naval Medical Research Unit Number 3, for providing training and facilitating the use of gel electrophoresis and Western blot in her lab. The authors would also like to acknowledge engineer Ahmed Gala El-Din, Faulty of Engineering, Ain Shams University, and Mr Mohamed El Tabbal, sixth-year medical student, Faculty of Medicine, Ain Shams University, for developing the OFT analysis software and allowing the authors the opportunity for a free trial version.

Disclosure

The authors report no conflicts of interest in this work.