Effects of ketamine on lipopolysaccharide-induced depressive-like behavior and the expression of inflammatory cytokines 
in the rat prefrontal cortex

Yang,Chun; Shen,Jiang; Hong,Tao; Hu,Ting-Ting; Li,Zhang-Jun; Zhang,Hai-Tao; Zhang,Yong-Jun; Zhou,Zhi-Qiang; Yang,Jian-Jun

doi:10.3892/mmr.2013.1600

September 2013 Volume 8 Issue 3

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September 2013 Volume 8 Issue 3

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Article

Effects of ketamine on lipopolysaccharide-induced depressive-like behavior and the expression of inflammatory cytokines in the rat prefrontal cortex

Authors:
- Chun Yang
- Jiang Shen
- Tao Hong
- Ting-Ting Hu
- Zhang-Jun Li
- Hai-Tao Zhang
- Yong-Jun Zhang
- Zhi-Qiang Zhou
- Jian-Jun Yang
View Affiliations / Copyright

Affiliations: Department of Anesthesiology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China
Pages: 887-890
|
Published online on: July 24, 2013

https://doi.org/10.3892/mmr.2013.1600
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Abstract

The present study was designed to investigate the effects of ketamine on lipopolysaccharide (LPS)-induced depressive-like behavior and the expression of inflammatory cytokines in the rat prefrontal cortex. Thirty male Wistar rats were randomly divided into 3 groups (n=10): saline group (S group), LPS only group (L group) and LPS plus ketamine group (LK group). A forced swimming test (FST) was performed. On the first day, rats were placed into water for 15 min. Twenty-four hours later, rats were treated again as in the first test for a 5 min session, and the immobility time was recorded. The prefrontal cortex was harvested for the determination of the interleukin (IL)‑1β, IL-6 and IL-10 levels. Compared with the S group, rats in the L group had significantly increased immobility time in the FST and expression of IL-1β and IL-6, and significantly decreased expression of IL-10 in the prefrontal cortex (P<0.05). However, rats in the LK group had significantly decreased immobility times in the FST and expression of IL-1β and IL-6, and significantly increased expression of IL-10 in the prefrontal cortex compared with the L group (P<0.05). Ketamine can alleviate LPS-induced depressive-like behavior, and its effect is likely associated with changes in the expression of inflammatory cytokines in the rat prefrontal cortex.

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1	Aan Het Rot M, Zarate CA Jr, Charney DS and Mathew SJ: Ketamine for depression: where do we go from here? Biol Psychiatry. 72:537–547. 2012.PubMed/NCBI
2	Mathew SJ, Shah A, Lapidus K, et al: Ketamine for treatment-resistant unipolar depression: current evidence. CNS Drugs. 26:189–204. 2012. View Article : Google Scholar : PubMed/NCBI
3	Machado-Vieira R, Salvadore G, Diazgranados N and Zarate CA Jr: Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther. 123:143–150. 2009. View Article : Google Scholar : PubMed/NCBI
4	Krystal JH: Ketamine and the potential role for rapid-acting antidepressant medications. Swiss Med Wkly. 137:215–216. 2007.PubMed/NCBI
5	Li N, Lee B, Liu RJ, et al: mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 329:959–964. 2010. View Article : Google Scholar : PubMed/NCBI
6	Catena-Dell’Osso M, Bellantuono C, Consoli G, Baroni S, Rotella F and Marazziti D: Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development? Curr Med Chem. 18:245–255. 2011.PubMed/NCBI
7	Hayley S, Poulter MO, Merali Z and Anisman H: The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity. Neuroscience. 135:659–678. 2005. View Article : Google Scholar : PubMed/NCBI
8	Raedler TJ: Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatry. 24:519–525. 2011.PubMed/NCBI
9	De Berardis D, Conti CM, Serroni N, et al: The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature. Int J Immunopathol Pharmacol. 23:417–422. 2010.PubMed/NCBI
10	Song C and Wang H: Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry. 35:760–768. 2011. View Article : Google Scholar : PubMed/NCBI
11	Hosseini M, Zakeri S, Khoshdast S, et al: The effects of Nigella sativa hydro-alcoholic extract and thymoquinone on lipopolysaccharide-induced depression like behavior in rats. J Pharm Bioallied Sci. 4:219–225. 2012.
12	Park SE, Lawson M, Dantzer R, Kelley KW and McCusker RH: Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide. J Neuroinflammation. 8:1792011. View Article : Google Scholar : PubMed/NCBI
13	Loix S, De Kock M and Henin P: The anti-inflammatory effects of ketamine: state of the art. Acta Anaesthesiol Belg. 62:47–58. 2011.PubMed/NCBI
14	Sun J, Zhou ZQ, Lv R, Li WY and Xu JG: Ketamine inhibits LPS-induced calcium elevation and NF-kappa B activation in monocytes. Inflamm Res. 53:304–308. 2004.PubMed/NCBI
15	Yang JJ, Zhou ZQ and Yang C: Letter to the editor: does ketamine exert a fast-acting antidepressant effect via inhibition of pro-inflammatory cytokines? Psychol Med. 41:17872011. View Article : Google Scholar : PubMed/NCBI
16	Porsolt RD, Le Pichon M and Jalfre M: Depression: a new animal model sensitive to antidepressant treatments. Nature. 266:730–732. 1977. View Article : Google Scholar : PubMed/NCBI
17	Herzum I and Renz H: Inflammatory markers in SIRS, sepsis and septic shock. Curr Med Chem. 15:581–587. 2008. View Article : Google Scholar : PubMed/NCBI
18	Biswas SK and Lopez-Collazo E: Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol. 30:475–487. 2009. View Article : Google Scholar : PubMed/NCBI
19	Dunn AJ, Swiergiel AH and de Beaurepaire R: Cytokines as mediators of depression: what can we learn from animal studies? Neurosci Biobehav Rev. 29:891–909. 2005. View Article : Google Scholar : PubMed/NCBI
20	Kang A, Hao H, Zheng X, et al: Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy. J Neuroinflammation. 8:1002011. View Article : Google Scholar : PubMed/NCBI
21	Taniguchi T and Yamamoto K: Anti-inflammatory effects of intravenous anesthetics on endotoxemia. Mini Rev Med Chem. 5:241–245. 2005. View Article : Google Scholar : PubMed/NCBI
22	Yang C, Li WY, Yu HY, et al: Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex. J Biomed Biotechnol. 2012:1756192012. View Article : Google Scholar
23	Yang C, Hong T, Shen J, et al: Ketamine exerts antidepressant effects and reduces IL-1β and IL-6 levels in rat prefrontal cortex and hippocampus. Exp Ther Med. 5:1093–1096. 2013.PubMed/NCBI