Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus
Abstract
Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor. Clinical findings point to a rapid onset of action for ketamine on the treatment of major depression. Considering that classic antidepressants may take long-lasting time to exhibit their main therapeutic effects, the present study aims to compare the behavioral effects and the BDNF hippocampus levels of acute administration of ketamine and imipramine in rats. To this aim, rats were acutely treated with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and animal behavioral was assessed in the forced swimming and open-field tests. Afterwards, BDNF protein hippocampal levels were assessed in imipramine- and ketamine-treated rats by ELISA-sandwich assay. We observed that ketamine at the doses of 10 and 15 mg/kg, and imipramine at 20 and 30 mg/kg reduced immobility time compared to saline group, without affecting locomotor activity. Interesting enough, acute administration of ketamine at the higher dose, but not imipramine, increased BDNF protein levels in the rat hippocampus. In conclusion, our findings suggest that the increase of hippocampal BDNF protein levels induced by ketamine might be necessary to produce a rapid onset of antidepressant action.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Acute ketamine that induces an antidepressant effect increases BDNF protein levels in the hippocampus.
“This data is in agreement with prior work showing that acute ketamine that induces an antidepressant effect increases BDNF protein levels in the hippocampus (Garcia et al., 2008).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Garcia et al., 2008
Cites
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766 · see citing works
Decreased serum brain-derived neurotrophic factor levels in major depressed patients
Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., & Aubry, J.-M. (2002) · Psychiatry Research · doi:10.1016/s0165-1781(02)00005-7 · Cited by 1,232 · see citing works
Role of neurotrophic factors in depression
CASTREN, E., VOIKAR, V, & RANTAMAKI, T. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.08.009 · Cited by 667 · see citing works
de Foubert, G., Carney, S. L., Robinson, C. S., Destexhe, E. J., Tomlinson, R., Hicks, C. A., Murray, T. K., Gaillard, J. P., Deville, C., Xhenseval, V., et al. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.06.054 · Cited by 249 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The molecular neurobiology of depression
Krishnan, V., & Nestler, E. J. (2008) · Nature · doi:10.1038/nature07455 · Cited by 2,889 · see citing works
Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127 · see citing works
Li, N., Liu, R.-J., Dwyer, J. M., Banasr, M., Lee, B., Son, H., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.015 · Cited by 1,082 · see citing works
BDNF - a key transducer of antidepressant effects
Björkholm, C., & Monteggia, L. M. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.034 · Cited by 958 · see citing works
“This data is in agreement with prior work showing that acute ketamine that induces an antidepressant effect increases BDNF protein levels in the hippocampus (Garcia et al., 2008).”
ResultLeonard, B., & Maes, M. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.12.005 · Cited by 805 · see citing works
Zarate, C. A., Brutsche, N. E., Ibrahim, L., Franco-Chaves, J., Diazgranados, N., Cravchik, A., Selter, J., Marquardt, C. A., Liberty, V., & Luckenbaugh, D. A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.010 · Cited by 811 · see citing works
Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression.
Newport, D. J., Carpenter, L. L., McDonald, W. M., Potash, J. B., Tohen, M., Nemeroff, C. B., & The APA Council of Research Task Force on Novel Biomarkers and Treatments (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15040465 · Cited by 598 · see citing works
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594 · see citing works
Self-citationNeuroinflammation and comorbidity of pain and depression
Walker, A. K., Kavelaars, A., Heijnen, C. J., & Dantzer, R. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008144 · Cited by 460 · see citing works
Walker, A. K., Budac, D. P., Bisulco, S., Lee, A. W., Smith, R. A., Beenders, B., Kelley, K. W., & Dantzer, R. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.71 · Cited by 432 · see citing works
Zhou, W., Wang, N., Yang, C., Li, X.-M., Zhou, Z.-Q., & Yang, J.-J. (2014) · European Psychiatry · doi:10.1016/j.eurpsy.2013.10.005 · Cited by 390 · see citing works
Ketamine: 50 Years of Modulating the Mind
Li, L., & Vlisides, P. E. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00612 · Cited by 385 · see citing works
Koike, H., Iijima, M., & Chaki, S. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.05.035 · Cited by 346 · see citing works
Maes, M., Fišar, Z., Medina, M., Scapagnini, G., Nowak, G., & Berk, M. (2012) · Inflammopharmacology · doi:10.1007/s10787-011-0111-7 · Cited by 325 · see citing works
Scheidegger, M., Walter, M., Lehmann, M., Metzger, C., Grimm, S., Boeker, H., Boesiger, P., Henning, A., & Seifritz, E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044799 · Cited by 282 · see citing works
Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants
Browne, C. A., & Lucki, I. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00161 · Cited by 285 · see citing works
An excitatory synapse hypothesis of depression
Thompson, S. M., Kallarackal, A. J., Kvarta, M. D., Van Dyke, A. M., LeGates, T. A., & Cai, X. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.03.003 · Cited by 265 · see citing works
Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor
Wei, Y., Chang, L., & Hashimoto, K. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01121-1 · Cited by 248 · see citing works
Memantine for the Treatment of Dementia: A Review on its Current and Future Applications
Folch, J., Busquets, O., Ettcheto, M., Sánchez-López, E., Castro-Torres, R. D., Verdaguer, E., Garcia, M. L., Olloquequi, J., Casadesús, G., Beas-Zarate, C., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170672 · Cited by 245 · see citing works
Glutamatergic Modulators: The Future of Treating Mood Disorders?
Zarate, C., Machado-Vieira, R., Henter, I., Ibrahim, L., Diazgranados, N., & Salvadore, G. (2010) · Harvard Review of Psychiatry · doi:10.3109/10673229.2010.511059 · Cited by 228 · see citing works
Belujon, P., & Grace, A. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.04.014 · Cited by 225 · see citing works
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah, C. G., Adams, T. G., Kelmendi, B., Esterlis, I., Sanacora, G., & Krystal, J. H. (2016) · Depression and Anxiety · doi:10.1002/da.22501 · Cited by 206 · see citing works
Widman, A. J., & McMahon, L. L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718883115 · Cited by 204 · see citing works
Ketamine elicits sustained antidepressant-like activity via a serotonin-dependent mechanism
Gigliucci, V., O’Dowd, G., Casey, S., Egan, D., Gibney, S., & Harkin, A. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3024-x · Cited by 177 · see citing works
Yang, C., Hu, Y.-M., Zhou, Z.-Q., Zhang, G.-F., & Yang, J.-J. (2013) · Upsala Journal of Medical Sciences · doi:10.3109/03009734.2012.724118 · Cited by 173 · see citing works
Ketamine as a Novel Antidepressant: From Synapse to Behavior
Murrough, J. W. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.244 · Cited by 172 · see citing works
Convergent Mechanisms Underlying Rapid Antidepressant Action
Zanos, P., Thompson, S. M., Duman, R. S., Zarate, C. A., & Gould, T. D. (2018) · CNS Drugs · doi:10.1007/s40263-018-0492-x · Cited by 171 · see citing works
Machado-Vieira, R., Manji, H. K., & Zarate, C. A. (2009) · The Neuroscientist · doi:10.1177/1073858409336093 · Cited by 171 · see citing works
Translating Glutamate: From Pathophysiology to Treatment
Javitt, D. C., Schoepp, D., Kalivas, P. W., Volkow, N. D., Zarate, C., Merchant, K., Bear, M. F., Umbricht, D., Hajos, M., Potter, W. Z., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002804 · Cited by 168 · see citing works
Donahue, R. J., Muschamp, J. W., Russo, S. J., Nestler, E. J., & Carlezon, W. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.12.014 · Cited by 161 · see citing works
Machado-Vieira, R., Yuan, P., Brutsche, N., DiazGranados, N., Luckenbaugh, D., Manji, H. K., & Zarate, C. A. (2009) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.08m04659 · Cited by 155 · see citing works
Fortunato, J. J., Réus, G. Z., Kirsch, T. R., Stringari, R. B., Stertz, L., Kapczinski, F., Pinto, J. P., Hallak, J. E., Zuardi, A. W., Crippa, J. A., et al. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.07.021 · Cited by 150 · see citing works
Self-citationAMPA receptor subunit 1 (GluR‐A) knockout mice model the glutamate hypothesis of depression
Chourbaji, S., Vogt, M. A., Fumagalli, F., Sohr, R., Frasca, A., Brandwein, C., Hörtnagl, H., Riva, M. A., Sprengel, R., & Gass, P. (2008) · The FASEB Journal · doi:10.1096/fj.08-106450 · Cited by 144 · see citing works
Mao, J., Li, T., Fan, D., Zhou, H., Feng, J., Liu, L., Zhang, C., & Wang, X. (2020) · BMC Psychiatry · doi:10.1186/s12888-019-2374-2 · Cited by 120 · see citing works
Orozco-Solis, R., Montellier, E., Aguilar-Arnal, L., Sato, S., Vawter, M. P., Bunney, B. G., Bunney, W. E., & Sassone-Corsi, P. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.02.1176 · Cited by 119 · see citing works
Aleksandrova, L. R., Wang, Y. T., & Phillips, A. G. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.07.007 · Cited by 114 · see citing works
Chronic dim light at night provokes reversible depression-like phenotype: possible role for TNF
Bedrosian, T. A., Weil, Z. M., & Nelson, R. J. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.96 · Cited by 112 · see citing works
Harmine and Imipramine Promote Antioxidant Activities in Prefrontal Cortex and Hippocampus
Réus, G. Z., Stringari, R. B., de Souza, B., Petronilho, F., Dal-Pizzol, F., Hallak, J. E., Zuardi, A. W., Crippa, J. A., & Quevedo, J. (2010) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.3.5.13109 · Cited by 110 · see citing works
Self-citationKadriu, B., Greenwald, M., Henter, I. D., Gilbert, J. R., Kraus, C., Park, L. T., & Zarate, C. A. (2021) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa087 · Cited by 99 · see citing works
Zomkowski, A. D. E., Engel, D., Gabilan, N. H., & Rodrigues, A. L. S. (2010) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2010.07.011 · Cited by 94 · see citing works
Novel glutamatergic agents for major depressive disorder and bipolar disorder
Machado-Vieira, R., Ibrahim, L., Henter, I. D., & Zarate, C. A. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.09.010 · Cited by 92 · see citing works
Ludka, F. K., Zomkowski, A. D. E., Cunha, M. P., Dal-Cim, T., Zeni, A. L. B., Rodrigues, A. L. S., & Tasca, C. I. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.05.005 · Cited by 92 · see citing works
Réus, G. Z., Stringari, R. B., Ribeiro, K. F., Luft, T., Abelaira, H. M., Fries, G. R., Aguiar, B. W., Kapczinski, F., Hallak, J. E., Zuardi, A. W., et al. (2011) · Acta Neuropsychiatrica · doi:10.1111/j.1601-5215.2011.00579.x · Cited by 86 · see citing works
Self-citationKang, M. J. Y., Hawken, E., & Vazquez, G. H. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.860882 · Cited by 77 · see citing works
Picard, N., Takesian, A. E., Fagiolini, M., & Hensch, T. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0341-9 · Cited by 71 · see citing works
Yang, X., Yang, Q., Wang, X., Luo, C., Wan, Y., Li, J., Liu, K., Zhou, M., & Zhang, C. (2014) · NeuroMolecular Medicine · doi:10.1007/s12017-014-8312-z · Cited by 69 · see citing works
Zhou, Z., Zhang, G., Li, X., Liu, X., Wang, N., Qiu, L., Liu, W., Zuo, Z., & Yang, J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-014-8798-2 · Cited by 64 · see citing works
Ketamine regulates the presynaptic release machinery in the hippocampus
Müller, H. K., Wegener, G., Liebenberg, N., Zarate, C. A., Popoli, M., & Elfving, B. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.03.008 · Cited by 61 · see citing works
Antidepressant-like behavioral effects of IGF-I produced by enhanced serotonin transmission
Hoshaw, B. A., Hill, T. I., Crowley, J. J., Malberg, J. E., Khawaja, X., Rosenzweig-Lipson, S., Schechter, L. E., & Lucki, I. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.07.023 · Cited by 60 · see citing works
du Jardin, K. G., Liebenberg, N., Cajina, M., Müller, H. K., Elfving, B., Sanchez, C., & Wegener, G. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00978 · Cited by 47 · see citing works
Amidfar, M., Réus, G. Z., Quevedo, J., & Kim, Y.-K. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.03.023 · Cited by 43 · see citing works
Self-citationPlasticity of synapses and reward circuit function in the genesis and treatment of depression
Thompson, S. M. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01422-1 · Cited by 40 · see citing works
Ren, L. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110910 · Cited by 23 · see citing works
Réus, G. Z., Stringari, R. B., Rezin, G. T., Fraga, D. B., Daufenbach, J. F., Scaini, G., Benedet, J., Rochi, N., Streck, E. L., & Quevedo, J. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-011-0718-2 · Cited by 23 · see citing works
Self-citationPérez de la Mora, M., Borroto-Escuela, D. O., Crespo-Ramírez, M., Rejón-Orantes, J. D. C., Palacios-Lagunas, D. A., Martínez-Mata, M. K., Sánchez-Luna, D., Tesoro-Cruz, E., & Fuxe, K. (2022) · Cells · doi:10.3390/cells11111826 · Cited by 21 · see citing works
Du Jardin, K. G., Müller, H. K., Sanchez, C., Wegener, G., & Elfving, B. (2017) · Synapse · doi:10.1002/syn.21940 · Cited by 20 · see citing works
Chen, M., Jin, J., Bi, H., Zhang, Y., Sun, M., Li, X., & Wang, Y. (2025) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2025.104502 · Cited by 14 · see citing works
- Authors
- Garcia, L. S. B., Comim, C. M., Valvassori, S. S., Réus, G. Z., Barbosa, L. M., Andreazza, A. C., Stertz, L., Fries, G. R., Gavioli, E. C., Kapczinski, F., & Quevedo, J.
- Affiliations
- Universidade do Extremo Sul Catarinense (BR)
- Universidade Federal do Rio Grande do Sul (BR)
- Corresponding author
- Quevedo, João
- ORCID
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 32
- Issue
- 1
- Pages
- 140-144
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2024636695
- Cited by
- 454
- References
- 4
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 17 · 2023: 25 · 2022: 18 · 2021: 23 · 2020: 31 · 2019: 29 · 2018: 36 · 2017: 32 · 2016: 37 · 2015: 37 · 2014: 24 · 2013: 27 · 2012: 25
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ketamine, imipramine, antidepressant-like effects, brain-derived neurotrophic factor, hippocampus, forced swim test, immobility time, locomotor activity, NMDA receptor antagonists, major depressive disorder
- MeSH terms
- Analysis of Variance, Animals, Antidepressive Agents, Behavior, Animal, Dose-Response Relationship, Drug, Hippocampus, Imipramine, Ketamine, Male, Swimming, Rats, Wistar, Brain-Derived Neurotrophic Factor, Immobility Response, Tonic, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
