title: N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: behavioral and biochemical analyses in rats.
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.
authors: Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Krakow, Poland.
authors: Irena
authors: I
authors: Smaga
authors: Bartosz
authors: B
authors: Pomierny
authors: Weronika
authors: W
authors: Krzyżanowska
authors: Lucyna
authors: L
authors: Pomierny-Chamioło
authors: Joanna
authors: J
authors: Miszkiel
authors: Ewa
authors: E
authors: Niedzielska
authors: Agata
authors: A
authors: Ogórka
authors: Małgorzata
authors: M
authors: Filip
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009830:Olfactory Bulb / Q000601:surgery; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D013482:Superoxide Dismutase; D007099:Imipramine; D000111:Acetylcysteine