Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines
Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
4 May 2017
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| In: |
European archives of psychiatry and clinical neuroscience
Year: 2017, Volume: 267, Issue: 8, Pages: 737-749 |
| ISSN: | 1433-8491 |
| DOI: | 10.1007/s00406-017-0807-9 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1007/s00406-017-0807-9 Verlag, Volltext: http://link.springer.com/article/10.1007/s00406-017-0807-9 
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| Author Notes: | Ivana Perić, Andrijana Stanisavljević, Peter Gass, Dragana Filipović |
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| 520 | |a Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS. The subcellular distributions of nuclear factor-κB (NF-κB), as well as, cytosolic IL-1β and IL-6 protein expression, were also determined. CSIS induced depressive- and anxiety-like behaviors, evidenced by a decrease in sucrose preference and an increase in the number of buried marbles. Moreover, CSIS compromised redox homeostasis, targeting enzymes such as GPx, CAT, GST, and caused NF-κB nuclear translocation with a concomitant increase in IL-6 protein expression, without an effect on IL-1β. Flx treatment reversed CSIS-induced depressive- and anxiety-like behaviors, modulated GSH-dependent defense by increasing GLR and GST activity, and suppressed NF-κB activation and cytosolic IL-6 protein expression in socially isolated rats. The present study suggests that changes in the GSH-dependent defense system, NF-κB activation and increased IL-6 protein expression may have a role in social isolation-induced changes in a rat model of depression and anxiety, and contributes to our understanding of the mechanisms that underlie the antidepressant and anti-inflammatory activity of Flx in socially isolated rats. | ||
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