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- Title
Effects of pentoxifylline, 7-nitroindazole, and imipramine on tumor necrosis factor-α and indoleamine 2,3-dioxygenase enzyme activity in the hippocampus and frontal cortex of chronic mild-stress-exposed rats.
- Authors
Mohamed, Bassim M. S. A.; Aboul-Fotouh, Sawsan; Ibrahim, Eman A.; Shehata, Hanan; Mansour, Amal A.; Yassin, Nemat A. Z.; El-Eraky, Wafaa; Abdel-Tawab, Ahmed M.
- Abstract
Objectives: This study aimed to investigate the role of tumor necrosis factor (TNF)-α and the neuronal nitric oxide synthase enzyme in dysregulation of indoleamine 2,3-dioxygenase (IDO) enzyme, and hence serotonin availability in chronic mild stress (CMS), an animal model of depression. Methods: Rats were divided into five groups: two control and CMS-exposed for 6 weeks, and another three groups exposed to CMS and administered pentoxifylline 50 mg/kg/day intraperitoneally, 7-nitroindazole 40 mg/kg/day subcutaneously, or imipramine 20 mg/kg/day intraperitoneally for the previous 3 CMS weeks. Rats were assessed for neurochemical and immunohistochemical abnormalities. Results: Pentoxifylline-, 7-nitroindazole-, and imipramine-treated rats showed amelioration of CMS-induced behavioral deficits that was accompanied by significant reduction in kynurenine/serotonin molar ratio and nitrates/nitrites in frontal cortex and hippocampus. In the pentoxifylline and 7-nitroindazole groups, serum TNF-α was reduced relative to the CMS group (18.54 ± 0.85 and 19.16 ± 1.54 vs 26.20 ± 1.83 pg/mL, respectively; P , 0.05). Exposure to CMS increased TNF-α and IDO immunohistochemical staining scores in both hippocampus and midbrain raphe nuclei. 7-Nitroindazole and pentoxifylline significantly (P < 0.05) reduced TNF-α immunostaining in hippocampus and raphe nuclei, with significant (P < 0.01) reduction of IDO immunostaining in raphe nuclei. Likewise, imipramine reduced TNF-α immunostaining (P < 0.05) in hippocampus. Conclusion: Neuronal nitric oxide synthase and TNF-α may play a concerted role in modulating IDO enzyme activity in CMS-exposed rats and provide additional evidence for possible alternative approaches to switch the neurobiological processes in depression.
- Subjects
PENTOXIFYLLINE; IMIPRAMINE; TUMOR necrosis factors; INDOLEAMINE 2,3-dioxygenase; PSYCHOLOGICAL stress; LABORATORY rats
- Publication
Neuropsychiatric Disease & Treatment, 2013, Vol 9, p697
- ISSN
1176-6328
- Publication type
Article
- DOI
10.2147/NDT.S41020