Chronic administration of Infliximab (TNF-α Inhibitor) decreases depression and anxiety-like behaviour in rat model of chronic mild stress
Open accessAbstract
Pro‐inflammatory cytokines have been proposed to be associated with the pathogenesis of depression. Consistent with this notion, several clinical observations have suggested the antidepressant efficacy of TNF‐α inhibitors in patients with chronic inflammatory diseases. In this study, we evaluated the antidepressant and anxiolytic effects of chronic TNF‐α inhibitor (infliximab, 5 mg/kg, i.p., weekly) administration in the chronic mild stress (CMS) model of depression. Rats were divided into three groups: saline‐control (no stress), saline‐CMS, and infliximab‐CMS. Rats in the latter two groups were exposed to CMS for 8 weeks. Saline (former two groups) or infliximab was injected weekly during this period. After CMS, total locomotor activity, anxiety‐like behaviour and depression‐like behaviours were evaluated using automated locomotor activity cage, elevated plus maze (EPM), and sucrose preference (SPT) and forced swimming (FS) tests, respectively. As expected, the saline‐CMS group exhibited higher depression‐like behaviours in FS and SPT tests compared with the saline‐control group. There were no differences between these two groups in terms of the anxiety‐like behaviour or total locomotor activity. Infliximab reduced the depression‐like behaviour of CMS rats compared with saline‐CMS group, and anxiety‐like behaviour of CMS rats compared with saline‐CMS and saline‐control groups. Our findings suggest that chronic and systemic TNF‐α inhibition reduced depression and anxiety‐like behaviour in the CMS model of depression in rats.
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Infliximab reduced depression and anxiety-like behavior in mildly stressed rats compared with controls and saline administration.
“a study that demonstrated similar effects of Infliximab on mildly stressed rats including decreased depression and anxiety-like behavior when compared to controls and saline administration (Karson et al., 2013).”
From A Review of the Relationship between Proinflammatory Cytokines and Major Depressive Disorder (2014) · cites this paper as Karson et al., 2013
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Cites
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729 · see citing works
Depression: a new animal model sensitive to antidepressant treatments
PORSOLT, R. D., LE PICHON, M., & JALFRE, M. (1977) · Nature · doi:10.1038/266730a0 · Cited by 4,451 · see citing works
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848 · see citing works
Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766 · see citing works
Willner, P. (1997) · Psychopharmacology · doi:10.1007/s002130050456 · Cited by 1,832 · see citing works
Willner, P. (2005) · Neuropsychobiology · doi:10.1159/000087097 · Cited by 1,605 · see citing works
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365 · see citing works
Chronic mild stress-induced anhedonia: A realistic animal model of depression
Willner, P., Muscat, R., & Papp, M. (1992) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80194-0 · Cited by 1,160 · see citing works
Tyring, S., Gottlieb, A., Papp, K., Gordon, K., Leonardi, C., Wang, A., Lalla, D., Woolley, M., Jahreis, A., Zitnik, R., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(05)67763-x · Cited by 1,069 · see citing works
Maes, M., Yirmyia, R., Noraberg, J., Brene, S., Hibbeln, J., Perini, G., Kubera, M., Bob, P., Lerer, B., & Maj, M. (2009) · Metabolic Brain Disease · doi:10.1007/s11011-008-9118-1 · Cited by 894 · see citing works
Leonard, B., & Maes, M. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.12.005 · Cited by 805 · see citing works
Depression and anxiety in inflammatory bowel disease: A review of comorbidity and management
Graff, L. A., Walker, J. R., & Bernstein, C. N. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20873 · Cited by 586 · see citing works
Cytokines and psychopathology: Lessons from interferon-α
Capuron, L., & Miller, A. H. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.02.009 · Cited by 562 · see citing works
Glucocorticoids, cytokines and brain abnormalities in depression
Zunszain, P. A., Anacker, C., Cattaneo, A., Carvalho, L. A., & Pariante, C. M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.04.011 · Cited by 554 · see citing works
The blood-brain barrier and immune function and dysfunction
Banks, W. A., & Erickson, M. A. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.031 · Cited by 523 · see citing works
A trans-dimensional approach to the behavioral aspects of depression
Bessa, J. M. (2009) · Frontiers in Behavioral Neuroscience · doi:10.3389/neuro.08.001.2009 · Cited by 469 · see citing works
Depression: an inflammatory illness?: Figure 1
Krishnadas, R., & Cavanagh, J. (2012) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2011-301779 · Cited by 392 · see citing works
Tuglu, C., Kara, S. H., Caliyurt, O., Vardar, E., & Abay, E. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1566-z · Cited by 391 · see citing works
Th1, Th2, and Th3 cytokine alterations in major depression
MYINT, A., LEONARD, B., STEINBUSCH, H., & KIM, Y. (2005) · Journal of Affective Disorders · doi:10.1016/j.jad.2005.07.008 · Cited by 371 · see citing works
Mikovа, O. E., Yakimova, R., Bosmans, E., Kenis, G., & Maes, M. H. J. (2001) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(01)00081-5 · Cited by 299 · see citing works
The Kynurenine Pathway Modulates Neurodegeneration in a Drosophila Model of Huntington's Disease
Campesan, S., Green, E. W., Breda, C., Sathyasaikumar, K. V., Muchowski, P. J., Schwarcz, R. M., Kyriacou, C. P., & Giorgini, F. (2011) · Current Biology · doi:10.1016/j.cub.2011.04.028 · Cited by 261 · see citing works
Pollak, Y., & Yirmiya, R. (2002) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145702003152 · Cited by 215 · see citing works
Menter, A., Augustin, M., Signorovitch, J., Yu, A. P., Wu, E. Q., Gupta, S. R., Bao, Y., & Mulani, P. M. (2010) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2009.07.022 · Cited by 197 · see citing works
Connor, T., Song, C., Leonard, B. E., Merali, Z., & Anisman, H. (1998) · Neuroscience · doi:10.1016/s0306-4522(97)00533-2 · Cited by 195 · see citing works
Brustolim, D., Ribeiro‐dos‐Santos, R., Kast, R. E., Altschuler, E. L., & Soares, M. B. P. (2006) · International Immunopharmacology · doi:10.1016/j.intimp.2005.12.007 · Cited by 195 · see citing works
Song, C., Halbreich, U. M., Han, C., Leonard, B. E., & Luo, H. (2009) · Pharmacopsychiatry · doi:10.1055/s-0029-1202263 · Cited by 187 · see citing works
Farooq, R. K., Isingrini, E., Tanti, A., Guisquet, A. L., Arlicot, N., Minier, F., Leman, S., Chalon, S., Belzung, C., & Camus, V. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.03.020 · Cited by 177 · see citing works
Depression research: where are we now?
Lee, S., Jeong, J., Kwak, Y., & Park, S. K. (2010) · Molecular Brain · doi:10.1186/1756-6606-3-8 · Cited by 170 · see citing works
Comorbid depression in rheumatoid arthritis: Pathophysiology and clinical implications
Bruce, T. O. (2008) · Current Psychiatry Reports · doi:10.1007/s11920-008-0042-1 · Cited by 149 · see citing works
What are the risks of biologic therapy in rheumatoid arthritis? An update on safety.
Weisman, M. H. (2002) · PubMed · Cited by 138 · see citing works
Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat
Zhang, Y., Gu, F., Chen, J., & Dong, W. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.095 · Cited by 122 · see citing works
Psoriasis, a model of dermatologic psychosomatic disease: psychiatric implications and treatments
Rieder, E. A., & Tausk, F. (2011) · International Journal of Dermatology · doi:10.1111/j.1365-4632.2011.05071.x · Cited by 117 · see citing works
Spike–wave discharges are necessary for the expression of behavioral depression‐like symptoms
Sarkisova, K. Y., Kuznetsova, G. D., Куликов, М. А., & van Luijtelaar, G. (2009) · Epilepsia · doi:10.1111/j.1528-1167.2009.02260.x · Cited by 115 · see citing works
Vagotomy attenuates the behavioural but not the pyrogenic effects of interleukin-1 in rats
Luheshi, G. N., Bluthé, R.-M., Rushforth, D. A., MULCAHY, N., Konsman, J. P., Goldbach, M., & Dantzer, R. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00231-9 · Cited by 106 · see citing works
Long-lasting effects of chronic rTMS to treat chronic rodent model of depression.
Feng, S.-F., Shi, T.-R., Fan-Yang, Wang, W.-N., Chen, Y.-C., & Tan, Q.-R. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.04.019 · Cited by 100 · see citing works
Hattori, S., Hashimoto, R., Miyakawa, T., Yamanaka, H., Maeno, H., Wada, K., & Kunugi, H. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.02.036 · Cited by 94 · see citing works
Immune-To-Brain Signaling: How Important are the Blood–Brain Barrier-independent Pathways?
Quan, N. (2008) · Molecular Neurobiology · doi:10.1007/s12035-008-8026-z · Cited by 94 · see citing works
Sharma, H. S., Ali, S. F., Tian, Z. R., et al. (2009) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2009.gr10 · Cited by 86 · see citing works
Vitale, G., Ruggieri, V., Filaferro, M., Frigeri, C., Alboni, S., Tascedda, F., Brunello, N., Guerrini, R., Cifani, C., & Massi, M. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1646-9 · Cited by 77 · see citing works
Lack of aggression and anxiolytic-like behavior in TNF receptor (TNF-R1 and TNF-R2) deficient mice
Patel, A., Siegel, A., & Zalcman, S. S. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.05.005 · Cited by 76 · see citing works
Pulsed Light Irradiation Improves Behavioral Outcome in a Rat Model of Chronic Mild Stress
Wu, X., Alberico, S. L., Moges, H., Taboada, L. H. D., Tedford, C. E., & Anders, J. J. (2012) · Lasers in Surgery and Medicine · doi:10.1002/lsm.22004 · Cited by 51 · see citing works
Prager, G., Hadamitzky, M., Engler, A., Doenlen, R., Wirth, T., Pacheco‐López, G., Krügel, U., Schedlowski, M., & Engler, H. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9373-0 · Cited by 44 · see citing works
Favorable response to subcutaneous administration of infliximab in rats with experimental colitis
Triantafillidis, J. K. (2005) · World Journal of Gastroenterology · doi:10.3748/wjg.v11.i43.6843 · Cited by 39 · see citing works
Vécsei, L., & Beal, M. F. (1990) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(90)90043-h · Cited by 38 · see citing works
Anxiogenic activity of quinolinic acid and kynurenine in the social interaction test in mice
Lapin, I. P., Mutovkina, L. G., Ryzov, I. V., et al. (1996) · Journal of Psychopharmacology · doi:10.1177/026988119601000312 · Cited by 32 · see citing works
de Klerk, O. L., Bosker, F. J., Willemsen, A. T. M., van Waarde, A., Visser, A. K. D., de Jager, T., Dagytė, G., den Boer, J. A., Dierckx, R., & Meerlo, P. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881109349840 · Cited by 32 · see citing works
Li, Y., ZHENG, X., Liang, J., & Peng, Y. (2010) · Behavioural Processes · doi:10.1016/j.beproc.2010.01.020 · Cited by 31 · see citing works
Infliximab for patients with plaque psoriasis and severe psychiatric comorbidity
Id, B., Hyphantis, T., Gamvroulia, C., et al. (2007) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2007.02310.x · Cited by 28 · see citing works
Gimsa, U., Kanitz, E., Otten, W., Tuchscherer, M., Tuchscherer, A., & Ibrahim, S. M. (2012) · Cytokine · doi:10.1016/j.cyto.2012.04.001 · Cited by 22 · see citing works
Schaalan, M. F., & Nassar, N. N. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0486-2 · Cited by 21 · see citing works
Güzel, A., Güzel, A., Günaydın, M., et al. (2012) · Experimental Lung Research · doi:10.3109/01902148.2012.659836 · Cited by 12 · see citing works
Infliximab rescue of efalizumab withdrawal flare and psoriasis‐precipitated depression
Yip, L., Harrison, S., & Foley, P. A. (2008) · Australasian Journal of Dermatology · doi:10.1111/j.1440-0960.2008.00487.x · Cited by 10 · see citing works
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- Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry 2012;83:495-502.
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Köhler, O., Benros, M. E., Nordentoft, M., Farkouh, M. E., Iyengar, R. L., Mors, O., & Krogh, J. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1611 · Cited by 941 · see citing works
A Review of the Relationship between Proinflammatory Cytokines and Major Depressive Disorder
Young, J. J., Bruno, D., & Pomara, N. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.07.032 · Cited by 422 · see citing works
Role of Adiposity-Driven Inflammation in Depressive Morbidity
Capuron, L., Lasselin, J., & Castanon, N. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.123 · Cited by 182 · see citing works
Cheng, Y., Pardo, M., Armini, R. D. S., Martinez, A., Mouhsine, H., Zagury, J.-F., Jope, R. S., & Beurel, E. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.12.012 · Cited by 174 · see citing works
Bortolato, B., F. Carvalho, A., K. Soczynska, J., I. Perini, G., & S. McIntyre, R. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150630171433 · Cited by 142 · see citing works
The role of neuroinflammation on pathogenesis of affective disorders
Rhie, S. J., Jung, E.-Y., & Shim, I. (2020) · Journal of Exercise Rehabilitation · doi:10.12965/jer.2040016.008 · Cited by 126 · see citing works
Majidi, J., Kosari-Nasab, M., & Salari, A.-A. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.10.009 · Cited by 109 · see citing works
Adu, M. K., Shalaby, R., Chue, P., & Agyapong, V. I. O. (2022) · Behavioral Sciences · doi:10.3390/bs12060195 · Cited by 31 · see citing works
Astrocytic TNFα regulates the behavioral response to antidepressants
Duseja, R., Heir, R., Lewitus, G. M., Altimimi, H. F., & Stellwagen, D. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.09.012 · Cited by 25 · see citing works
- Authors
- Karson, A., Demirtaş, T., Bayramgürler, D., Balcı, F., & Utkan, T.
- Affiliations
- Kocaeli Üniversitesi (TR)
- Department of Pharmacology Medical School, Kocaeli University Kocaeli Turkey
- Koç University (TR)
- Corresponding author
- Karson, Ayşe
- Venue
- Basic & Clinical Pharmacology & Toxicology
- Publisher
- Wiley
- Published
- 2013-01-19
- Volume
- 112
- Issue
- 5
- Pages
- 335-340
- ISSN
- 1742-7835 (ISSN-L)
- 1742-7843
- OpenAlex
- W2109172889
- Cited by
- 143
- References
- 52
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 20 · 2020: 16 · 2019: 13 · 2018: 7 · 2017: 7 · 2016: 18 · 2015: 8 · 2014: 9 · 2013: 7
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Basic & Clinical Pharmacology & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Kocaeli Üniversitesi - AVESİS (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- infliximab, anti-TNF therapy, depression, anxiety-like behavior, chronic mild stress, antidepressant effects, anxiolytic effects, inflammatory cytokines, chronic inflammation, forced swim test, sucrose preference test, elevated plus maze, locomotor activity
- MeSH terms
- Infliximab, Animals, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, Anxiety, Behavior, Animal, Chronic Disease, Depression, Disease Models, Animal, Food Preferences, Male, Motor Activity, Stress, Physiological, Sucrose, Swimming, Rats, Wistar, Maze Learning, Rats
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