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Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice
- Source :
- Behavioural brain research. 344
- Publication Year :
- 2017
-
Abstract
- Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder. Chronic administration of corticosterone (CORT) to rodents is used to mimic the stress associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a well-established feature found in depressive patients. Recently, preclinical studies have demonstrated the antidepressant potential of histone deacetylase (HDAC) inhibitors. So, we examined the antidepressant potential of vorinostat (VOR), a HDAC inhibitor against CORT injections in male mice. VOR (25 mg/kg; intraperitoneal) and fluoxetine (FLX) (15 mg/kg; oral) treatments were provided to CORT administered mice. At the end of dosing schedule, neurobehavioral tests were conducted; followed by mechanistic evaluation through biochemical analysis, RTPCR and western blot in serum and hippocampus. Neurobehavioral tests revealed the development of anxiety/depressive-like behavior in CORT mice as compared to the vehicle control. Depressive-mice showed concomitant HPA axis dysregulation as observed from the significant increase in serum CORT and ACTH. Chronic CORT administration was found to significantly increase hippocampal malondialdehyde (MDA) and iNOS levels while lowering glutathione (GSH) content, as compared to vehicle control. VOR treatment, in a similar manner to the classical antidepressant FLX, significantly ameliorated anxiety/depressive-like behavior along with HPA axis alterations induced by CORT. The antidepressant-like ability of drug treatments against chronic CORT induced stress model, as revealed in our study, may be due to their potential to mitigate inflammatory damage and oxidative stress via modulation of hippocampal NF-κB p65, COX-2, HDAC2 and phosphorylated JNK levels.
- Subjects :
- 0301 basic medicine
Male
endocrine system
medicine.medical_specialty
Anti-Inflammatory Agents
Anxiety
medicine.disease_cause
Hydroxamic Acids
Hippocampus
Antioxidants
03 medical and health sciences
Behavioral Neuroscience
chemistry.chemical_compound
Mice
Random Allocation
0302 clinical medicine
Corticosterone
Internal medicine
Fluoxetine
medicine
Animals
Chronic stress
Vorinostat
Inflammation
Depressive Disorder
business.industry
medicine.disease
Malondialdehyde
Antidepressive Agents
Disease Models, Animal
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
Chronic Disease
Major depressive disorder
Antidepressant
business
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Oxidative stress
Stress, Psychological
medicine.drug
Subjects
Details
- ISSN :
- 18727549
- Volume :
- 344
- Database :
- OpenAIRE
- Journal :
- Behavioural brain research
- Accession number :
- edsair.doi.dedup.....cd58209efa711670f59e75dd32fd385d