Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain
Abstract
There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na(+)/K(+) ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
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?
Treatment with mood stabilizers increases BDNF levels in prefrontal cortex and hippocampus of animals by inducing promoter IV-driven expression.
“It is known that treatment with mood stabilizers increases BDNF levels in prefrontal cortex and hippocampus of animals by inducing promoter IV-driven expression [90, 91].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [91]
Cites
Neurotrophins: Roles in Neuronal Development and Function
Huang, E. J., & Reichardt, L. F. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.677 · Cited by 4,394 · see citing works
Yatham, L. N., & Malhi, G. S. (2011) · Oxford University Press eBooks · doi:10.1093/med/9780199562305.001.0001 · Cited by 3,515 · see citing works
Davenport, Y. B., Adland, M. L., Gold, P. W., & Goodwin, F. K. (1984) · The Lancet · doi:10.1016/s0140-6736(84)92810-1 · Cited by 2,925 · see citing works
Papageorgis, D. (1991) · Behaviour Research and Therapy · doi:10.1016/0005-7967(91)90087-j · Cited by 1,542 · see citing works
The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings
Strakowski, S. M., DelBello, M. P., & Adler, C. M. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001585 · Cited by 818 · see citing works
The neurotrophin hypothesis for synaptic plasticity
Schinder, A. F. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01672-6 · Cited by 729 · see citing works
The Role of the Extracellular Signal-Regulated Kinase Signaling Pathway in Mood Modulation
Einat, H., Yuan, P., Gould, T. D., Li, J., Du, J., Zhang, L., Manji, H. K., & Chen, G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-19-07311.2003 · Cited by 475 · see citing works
Belmaker, R. H. (2004) · New England Journal of Medicine · doi:10.1056/nejmra035354 · Cited by 473 · see citing works
Cunha, A. B. M., Frey, B. N., Andreazza, A. C., Goi, J. D., Rosa, A. R., Gonçalves, C. A., Santin, A. M. P., & Kapczinski, F. P. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.12.085 · Cited by 391 · see citing works
Self-citationYatham, L. N., Kennedy, S. H., O'Donovan, C., Parikh, S., MacQueen, G., McIntyre, R., Sharma, V., Silverstone, P., Alda, M., Baruch, P., et al. (2005) · Bipolar Disorders · doi:10.1111/j.1399-5618.2005.00219.x · Cited by 388 · see citing works
Fukumoto, T., Morinobu, S., Okamoto, Y., Kagaya, A., & Yamawaki, S. (2001) · Psychopharmacology · doi:10.1007/s002130100871 · Cited by 377 · see citing works
Cellular Plasticity Cascades in the Pathophysiology and Treatment of Bipolar Disorder
Schloesser, R. J., Huang, J. Y., Klein, P. S., & Manji, H. K. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301575 · Cited by 256 · see citing works
Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania
Frey, B. N., Andreazza, A. C., Ceresér, K. M. M., Martins, M. R., Valvassori, S. S., Réus, G. Z., Quevedo, J., & Kapczinski, F. P. (2006) · Life Sciences · doi:10.1016/j.lfs.2006.01.002 · Cited by 239 · see citing works
Self-citationGlycogen synthase kinase‐3β, mood stabilizers, and neuroprotection
Li, X., Bijur, G. N., & Jope, R. S. (2002) · Bipolar Disorders · doi:10.1034/j.1399-5618.2002.40201.x · Cited by 238 · see citing works
Lithium neuroprotection: molecular mechanisms and clinical implications
Rowe, M. K., & Chuang, D. (2004) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399404008385 · Cited by 194 · see citing works
Perspectives for the development of animal models of bipolar disorder
Machado-Vieira, R., Kapczinski, F., & Soares, J. C. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2003.10.015 · Cited by 158 · see citing works
Self-citationA common thread for pain and memory synapses? Brain-derived neurotrophic factor and trkB receptors
Malcangio, M., & Leßmann, V. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00025-7 · Cited by 154 · see citing works
Intracerebroventricular administration of ouabain as a model of mania in rats
El‐Mallakh, R. S., El-Masri, M. A., Huff, M. O., Li, X., Decker, S., & Levy, R. S. (2003) · Bipolar Disorders · doi:10.1034/j.1399-5618.2003.00053.x · Cited by 122 · see citing works
Animal models of bipolar disorder
Kato, T., Kubota, M., & Kasahara, T. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.03.003 · Cited by 78 · see citing works
Riegel, R. E., Valvassori, S. S., Elias, G. A., Réus, G. Z., Steckert, A. V., de Souza, B., Petronilho, F. C., Gavioli, E. C., Dal‐Pizzol, F., & Quevedo, J. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.05.003 · Cited by 75 · see citing works
Self-citationLithium prevents ouabain-induced behavioral changes
Li, R., El‐Mallakh, R. S., Harrison, L. T., et al. (1997) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815161 · Cited by 67 · see citing works
Mimicking human bipolar ion dysregulation models mania in rats
Herman, L., Hougland, T., & El‐Mallakh, R. S. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.04.001 · Cited by 66 · see citing works
Decker, S., Grider, G., Cobb, M., et al. (2000) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(99)00111-6 · Cited by 58 · see citing works
Persistent Hyperactivity Following a Single Intracerebroventricular Dose of Ouabain
Ruktanonchai, D., El-Mallakh, R. S., Li, R., & Levy, R. S. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(97)00457-5 · Cited by 56 · see citing works
Evaluation of neuroprotection by lithium and valproic acid against ouabain‐induced cell damage
Hennion, J., El-Masri, M. A., Huff, M. O., et al. (2002) · Bipolar Disorders · doi:10.1034/j.1399-5618.2002.01162.x · Cited by 54 · see citing works
Lithium increases nerve growth factor levels in the rat hippocampus in an animal model of mania
Frey, B. N., Andreazza, A. C., Rosa, A. R., Martins, M. R., Valvassori, S. S., Réus, G. Z., Hatch, J. P., Quevedo, J., & Kapczinski, F. P. (2006) · Behavioural Pharmacology · doi:10.1097/01.fbp.0000205013.59455.09 · Cited by 46 · see citing works
Self-citationThe Na,K-ATPase hypothesis for manic-depression. I. General considerations
El‐Mallakh, R. S. (1983) · Medical Hypotheses · doi:10.1016/0306-9877(83)90042-7 · Cited by 39 · see citing works
Efficacy of olanzapine and haloperidol in an animal model of mania
El‐Mallakh, R. S., Decker, S., Morris, M. W., Li, X., Huff, M. O., El-Masri, M. A., & Levy, R. S. (2006) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.04.003 · Cited by 38 · see citing works
Vajda, F. J. E. (2002) · Journal of Clinical Neuroscience · doi:10.1054/jocn.2002.1133 · Cited by 34 · see citing works
Hokin-Neaverson, M., & Jefferson, J. W. (2008) · Neuropsychobiology · doi:10.1159/000118587 · Cited by 32 · see citing works
Erythrocyte membrane sodium ? potassium adenosine triphosphatase activity in affective disorders
Reddy, P. L., Khanna, S., Subhash, M. N., et al. (1992) · Journal of Neural Transmission · doi:10.1007/bf01250673 · Cited by 26 · see citing works
Importance of rapid testing to combat the global threat of bird flu
Meijer, A. (2005) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.6.1.1 · Cited by 13 · see citing works
SCOTT, M., & Reading, H. W. (1978) · Biochemical Society Transactions · doi:10.1042/bst0060642 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation
Lima Giacobbo, B., Doorduin, J., Klein, H. C., Dierckx, R. A. J. O., Bromberg, E., & de Vries, E. F. J. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1283-6 · Cited by 750 · see citing works
Serum Brain-Derived Neurotrophic Factor Levels in Different Neurological Diseases
Ventriglia, M., Zanardini, R., Bonomini, C., Zanetti, O., Volpe, D., Pasqualetti, P., Gennarelli, M., & Bocchio-Chiavetto, L. (2013) · BioMed Research International · doi:10.1155/2013/901082 · Cited by 189 · see citing works
Varela, R. B., Valvassori, S. S., Lopes-Borges, J., Mariot, E., Dal-Pont, G. C., Amboni, R. T., Bianchini, G., & Quevedo, J. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.11.003 · Cited by 115 · see citing works
Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders
Galvez-Contreras, A. Y., Campos-Ordonez, T., Lopez-Virgen, V., Gomez-Plascencia, J., Ramos-Zuniga, R., & Gonzalez-Perez, O. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.08.004 · Cited by 112 · see citing works
Brand, S., Moller, M., & Harvey, B. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150307004545 · Cited by 95 · see citing works
Kuriyama, K., Honma, M., Yoshiike, T., & Kim, Y. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.07.045 · Cited by 36 · see citing works
Kirshenbaum, G. S., Burgess, C. R., Déry, N., Fahnestock, M., Peever, J. H., & Roder, J. C. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.12.011 · Cited by 33 · see citing works
- Authors
- Jornada, L. K., Moretti, M., Valvassori, S. S., Ferreira, C. L., Padilha, P. T., Arent, C. O., Fries, G. R., Kapczinski, F., & Quevedo, J.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Corresponding author
- Quevedo, João
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 44
- Issue
- 8
- Pages
- 506-510
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W1969674173
- Cited by
- 107
- References
- 33
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 7 · 2021: 25 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 10 · 2013: 10 · 2012: 7
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- mania, ouabain, bipolar disorder, brain-derived neurotrophic factor, lithium, valproic acid, mood stabilizers, hippocampus, amygdala, Na+/K+-ATPase inhibition, hyperlocomotion, animal model of mania, maintenance therapy
- MeSH terms
- Amygdala, Analysis of Variance, Animals, Bipolar Disorder, Disease Models, Animal, Drug Interactions, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Hippocampus, Male, Motor Activity, Ouabain, Valproic Acid, Rats, Wistar, Lithium Chloride, Antimanic Agents, Brain-Derived Neurotrophic Factor, 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
