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N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: behavioral and biochemical analyses in rats.
- Source :
-
Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2012 Dec 03; Vol. 39 (2), pp. 280-7. Date of Electronic Publication: 2012 Jul 20. - Publication Year :
- 2012
-
Abstract
- The growing body of evidence implicates the significance of oxidative stress in the pathophysiology of depression. The aim of this paper was to examine N-acetylcysteine (NAC) - a putative precursor of the most important tissue antioxidant glutathione - in an animal model of depression and in ex vivo assays to detect oxidative stress parameters. Imipramine (IMI), a classical and clinically-approved antidepressant drug was also under investigation. Male Wistar rats which underwent either bulbectomy (BULB; removal of the olfactory bulbs) or sham surgery (SHAM; olfactory bulbs were left undestroyed) were treated acutely or repeatedly with NAC (50-100mg/kg, ip) or IMI (10mg/kg, ip). Following 10-daily injections with NAC or IMI or their solvents, or 9-daily injections with a corresponding solvent plus acute NAC or acute IMI forced swimming test on day 10, and locomotor activity were performed; immediately after behavioral tests animals were decapitated. Biochemical tests (the total antioxidant capacity - TAC and the superoxide dismutase activity - SOD) were performed on homogenates in several brain structures. In behavioral studies, chronic (but not acute) administration of NAC resulted in a dose-dependent reduction in the immobility time seen only in BULB rats while chronic IMI produced a significant decrease in this parameter in both SHAM and BULB animals. On the other hand, chronic administration of NAC and IMI resulted in a significant increase in cellular antioxidant mechanisms (SOD activity) that reversed the effects of BULB in the frontal cortex, hippocampus and striatum. Our study further supports the antidepressant-like activity of NAC and links its effect as well as IMI actions with the enhancement of brain SOD activity.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Acetylcysteine administration & dosage
Acetylcysteine therapeutic use
Animals
Antidepressive Agents administration & dosage
Antidepressive Agents therapeutic use
Antioxidants therapeutic use
Brain drug effects
Brain metabolism
Depression drug therapy
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Imipramine pharmacology
Imipramine therapeutic use
Immobility Response, Tonic drug effects
Male
Motor Activity drug effects
Olfactory Bulb surgery
Oxidation-Reduction drug effects
Rats
Rats, Wistar
Superoxide Dismutase metabolism
Acetylcysteine pharmacology
Antidepressive Agents pharmacology
Antioxidants pharmacology
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1878-4216
- Volume :
- 39
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Progress in neuro-psychopharmacology & biological psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 22820675
- Full Text :
- https://doi.org/10.1016/j.pnpbp.2012.06.018