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.

Possible Involvement of the IL-6/JAK2/STAT3 Pathway in the Hypothalamus in Depressive-Like Behavior of Rats Exposed to Chronic Mild Stress

“…Interestingly, normalization of mRNA levels of members of the IL-6/JAK2/STAT3 pathway in the hypothalamus by administration of the SSRI paroxetine coincided with normalization of the depressive-like behaviors induced by CMS. Consistent with our results, a previous study found that paroxetine can reverse CMS-related depressive-like behavior, as seen in the FST and sucrose preference tests [62-64]. Previous studies revealed that paroxetine ameliorates depressive-like behaviors by improving brain inflammation and oxidative stress, reducing HPA axis hyperactivity, elevating BDNF (brain-derived neurotrophic factor) expression, and inhibiting serotonin and norepinephrine uptake [65-67].…”