The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling
Open accessAbstract
The mechanisms underlying the initiation/onset of, and the recovery from, depression are still largely unknown; views that neurogenesis in the hippocampus may be important for the pathogenesis and amelioration of depressive symptoms have gained currency over the years although the original evidence has been challenged. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 2 weeks of stress exposure, animals were treated with the antidepressants fluoxetine, imipramine, CP 156,526 or SSR 1494515, alone or combined with methylazoxymethanol, a cytostatic agent used to arrest neurogenesis. We found that antidepressants retain their therapeutic efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked. Instead, our experiments suggest re-establishment of neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus and prefrontal cortex, rather than neurogenesis, as the basis for the restoration of behavioral homeostasis by antidepressants.
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“In summary, the results of several experiments indicated very clearly that in rodents undergoing chronic mild stress or stress induced by corticosterone and whose neurogenesis has been ablated, some behavioral depression-like signs are ameliorated independently of neurogenesis, while some others are dependent (Airan et al., 2007;Bessa et al., 2009;Surget et al., 2008;David et al., 2009).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Bessa et al., 2009
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Furthermore, mounting evidence seems to indicate that neurogenesis might not be required for the therapeutic action of antidepressants (Bessa et al. 2009).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Bessa et al. 2009
In the citing paper
“Chronic, but not acute, administration of conventional antidepressants also reverses stress-induced dendritic atrophy in rodents[126]”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [126]
In the citing paper
“The sample sizes were based on previous published studies.9, 20”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [9]
In the citing paper
“at short-term, behavioral improvements induced by ADs rely on hippocampal neuronal remodeling,9”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [9]
In the citing paper
“Rats were subjected to a validated uCMS protocol for 6 weeks, as previously described9, 20, 23”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [9]
In the citing paper
“in line with previous studies demonstrating that ADs, including imipramine, reverse the shrinkage in dendritic branching induced by stress and allows the re-establishment of the normal neuronal network,9”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [9]
In the citing paper
“Besides boosting adult neurogenesis, fluoxetine treatment and further stress re-exposure also induced dendritic atrophy of the DG granule neurons, similar to the immediate effects induced by uCMS protocol in non-treated animals.9”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [9]
In the citing paper
“These residual changes, together with reported impairments in DG synaptic plasticity9, 28, 29 may account for the re-appearance of depressive, anxiety and cognitive deficits on uCMS re-exposure.”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [9]
In the citing paper
“In rodents, exposure to protocol of chronic stressors, that modeling some features of psychiatric disorders symptoms, induce alterations in dendritic remodeling and decrease adult hippocampal neurogenesis (38, 44, 99).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [99]
In the citing paper
“Other studies have concluded that long-term use of antidepressants can increase spine density or decrease atrophy of spines and dendrites after chronic stress.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [48]
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Citations
Cites
Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants
Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., et al. (2003) · Science · doi:10.1126/science.1083328 · Cited by 4,321
Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus
Malberg, J. E., Eisch, A. J., Nestler, E. J., & Duman, R. S. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09104.2000 · Cited by 3,111
Neurogenesis in the adult is involved in the formation of trace memories
Shors, T. J., Miesegaes, G. R., Beylin, A. V., Zhao, M., Rydel, T. A., & Gould, E. (2001) · Nature · doi:10.1038/35066584 · Cited by 2,014
Doetsch, F. K., García‐Verdugo, J. M., & Álvarez-Buylla, A. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-13-05046.1997 · Cited by 1,909
Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms
Pittenger, C., & Duman, R. S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301574 · Cited by 1,795
Willner, P. (2005) · Neuropsychobiology · doi:10.1159/000087097 · Cited by 1,605
New approaches to antidepressant drug discovery: beyond monoamines
Berton, O., & Nestler, E. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1846 · Cited by 1,589
Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A. M., & Fuchs, E. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-07-02492.1997 · Cited by 1,496
Álvarez-Buylla, A., & Lim, D. A. (2004) · Neuron · doi:10.1016/s0896-6273(04)00111-4 · Cited by 1,348
Untreated Depression and Hippocampal Volume Loss
Sheline, Y. I., Gado, M. H., & Kraemer, H. C. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.8.1516 · Cited by 1,180
Czéh, B., Michaelis, T., Watanabe, T., Frahm, J., de Biurrun, G., van Kampen, M., Bartolomucci, A., & Fuchs, E. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211427898 · Cited by 1,114
Harris, K. M., Jensen, F. E., & Tsao, B. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02685.1992 · Cited by 1,023
The antidepressant fluoxetine restores plasticity in the adult visual cortex
Vetencourt, J. F. M., Sale, A., Viegi, A., Baroncelli, L., De Pasquale, R., F. O'Leary, O., Castrén, E., & Maffei, L. (2008) · Science · doi:10.1126/science.1150516 · Cited by 890
Neurogenesis may relate to some but not all types of hippocampal‐dependent learning
Shors, T. J., Townsend, D. A., Zhao, M., Kozorovitskiy, Y., & Gould, E. (2002) · Hippocampus · doi:10.1002/hipo.10103 · Cited by 853
The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis
Kee, N., Sivalingam, S., Boonstra, R., & Wojtowicz, J. M. (2002) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(02)00007-9 · Cited by 785
Chronic stress alters dendritic morphology in rat medial prefrontal cortex
Cook, S. C., & Wellman, C. L. (2004) · Journal of Neurobiology · doi:10.1002/neu.20025 · Cited by 785
Radley, J. J., Sisti, H. M., Hao, J., Rocher, A. B., McCall, T., Hof, P. R., McEwen, B. S., & Morrison, J. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.01.006 · Cited by 769
Sairanen, M., Lucas, G., Ernfors, P., Castrén, M., & Castrén, E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3741-04.2005 · Cited by 763
Sousa, N., Lukoyanov, N. V., Madeira, M. D., Almeida, O. F. X., & Paula-Barbosa, M. M. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00050-6 · Cited by 758
Self-citationHow widespread is adult neurogenesis in mammals?
Gould, E. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2147 · Cited by 687
TrkB Regulates Hippocampal Neurogenesis and Governs Sensitivity to Antidepressive Treatment
Li, Y., Luikart, B. W., Birnbaum, S., Chen, J., Kwon, C.-H., Kernie, S. G., Bassel-Duby, R., & Parada, L. F. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.023 · Cited by 634
Neural stem cell proliferation is decreased in schizophrenia, but not in depression
Reif, A., Fritzen, S., Finger, M., Strobel, A., Lauer, M., Schmitt, A., & Lesch, K.-P. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001791 · Cited by 630
Cell adhesion molecules: signalling functions at the synapse
Dalva, M. B., McClelland, A. C., & Kayser, M. S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2075 · Cited by 620
A method for vibratome sectioning of Golgi–Cox stained whole rat brain
Gibb, R. L., & Kolb, B. E. (1998) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(97)00163-5 · Cited by 618
The prefrontal cortex as a key target of the maladaptive response to stress
Cerqueira, J. J., Mailliet, F., Almeida, O. F. X., Jay, T. M., & Sousa, N. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4372-06.2007 · Cited by 599
Self-citationCastrén, E. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1629 · Cited by 563
Bruel‐Jungerman, E., Laroche, S., & Rampon, C. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03875.x · Cited by 530
A role for adult TLX-positive neural stem cells in learning and behaviour
Zhang, C., Zou, Y., He, W., Gage, F. H., & Evans, R. M. (2008) · Nature · doi:10.1038/nature06562 · Cited by 523
Magnetic Resonance Spectroscopy Identifies Neural Progenitor Cells in the Live Human Brain
Manganas, L. N., Zhang, X., Li, Y., Hazel, R. D., Smith, S. D. B., Wagshul, M. E., Henn, F. A., Benveniste, H., Djurić, P. M., Enikolopov, G., et al. (2007) · Science · doi:10.1126/science.1147851 · Cited by 495
PSA-NCAM in mammalian structural plasticity and neurogenesis
Bonfanti, L. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.08.003 · Cited by 448
The effects of chronic antidepressant treatment in an animal model of anxiety
Bodnoff, S., Suranyi-Cadotte, B., Aitken, D., Quirion, R., & Meaney, M. (1988) · Psychopharmacology · doi:10.1007/bf00181937 · Cited by 437
High-speed imaging reveals neurophysiological links to behavior in an animal model of depression
Airan, R. D., Meltzer, L. A., Roy, M., Gong, Y., Chen, H., & Deisseroth, K. (2007) · Science · doi:10.1126/science.1144400 · Cited by 396
Glaser, E. M., & der Loos, H. V. (1981) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(81)90045-5 · Cited by 374
Holick, K. A., Lee, D. C., Hen, R., & Dulawa, S. C. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301399 · Cited by 326
Acute Stress-induced Changes in Hippocampal/Prefrontal Circuits in Rats: Effects of Antidepressants
Rocher, C. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhg122 · Cited by 307
Bekris, S., Antoniou, K., Daskas, S., & Papadopoulou-Daifoti, Z. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.01.005 · Cited by 281
Vollmayr, B., Simonis, C., Weber, S., Gass, P., & Henn, F. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00527-4 · Cited by 229
Overview of Diagnosis and Drug Treatments of Anxiety Disorders
Nutt, D. (2005) · CNS Spectrums · doi:10.1017/s1092852900009901 · Cited by 211
Sairanen, M., O’Leary, O. F., Knuuttila, J. E., & Castrén, E. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.069 · Cited by 206
Hippocampal volume reduction and HPA-system activity in major depression
Colla, M., Kronenberg, G., Deuschle, M., Meichel, K., Hagen, T., Bohrer, M., & Heuser, I. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.06.011 · Cited by 200
Is impaired neurogenesis relevant to the affective symptoms of depression?
Sapolsky, R. M. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.04.012 · Cited by 188
David, D. J. P., Klemenhagen, K. C., Holick, K. A., Saxe, M., Mendez‐David, I., Santarelli, L., Craig, D. A., Zhong, H., Swanson, C. J., Hegde, L. G., et al. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.109678 · Cited by 142
Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial prefrontal cortex
Varea, E., Blasco-Ibáñez, J. M., Gómez-Climent, M. Á., Castillo-Gómez, E., Crespo, C., Martínez-Guijarro, F. J., & Nácher, J. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301183 · Cited by 96
Lavretsky, H., Roybal, D. J., Ballmaier, M., Toga, A. W., & Kumar, A. A. (2005) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v66n0801 · Cited by 89
Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus
Dupret, D., Montaron, M., Drapeau, E., Aurousseau, C., Moal, M. L., Piazza, P., & Abrous, D. N. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04262.x · Cited by 73
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Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016) · Nature Medicine · doi:10.1038/nm.4050 · Cited by 1,750
Synaptic Dysfunction in Depression: Potential Therapeutic Targets
Duman, R. S., & Aghajanian, G. K. (2012) · Science · doi:10.1126/science.1222939 · Cited by 1,651
Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex
McEwen, B. S., Nasca, C., & Gray, J. D. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.171 · Cited by 1,574
Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation
Sahay, A., Scobie, K. N., Hill, A. S., O'Carroll, C. M., Kheirbek, M. A., Burghardt, N. S., Fenton, A. A., Dranovsky, A., & Hen, R. (2011) · Nature · doi:10.1038/nature09817 · Cited by 1,567
Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood
Anacker, C., & Hen, R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.45 · Cited by 1,014
Metadata
- Authors
- Bessa, J. M., Ferreira, D., Melo, I., Marques, F., Cerqueira, J. J., Palha, J. A., Almeida, O. F. X., & Sousa, N.
- Affiliations
- University of Minho (PT)
- Max Planck Society (DE)
- Corresponding author
- Sousa, N
- Venue
- Molecular Psychiatry
- Published
- 2008-11-04
- Volume
- 14
- Issue
- 8
- Pages
- 764-773
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W1983617759
- Cited by
- 598
- References
- 46
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 11 · 2023: 33 · 2022: 30 · 2021: 38 · 2020: 26 · 2019: 33 · 2018: 31 · 2017: 48 · 2016: 37 · 2015: 44 · 2014: 53 · 2013: 38 · 2012: 48
- FWCI
- 23.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Funders
- Pfizer
- Sanofi
- Fundação para a Ciência e a Tecnologia (PTDC/SAU-NEU/72699/2006)
- National Cancer Institute (N02-CB-07008)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- antidepressants, neurogenesis, hippocampus, neuronal remodeling, dendritic remodeling, synaptic plasticity, depression, chronic mild stress, fluoxetine, imipramine, methylazoxymethanol, anhedonia, learned helplessness, prefrontal cortex, neuroplasticity
- MeSH terms
- Affect, Analysis of Variance, Animals, Antidepressive Agents, Behavior, Animal, Depression, Drug Combinations, Fluoxetine, Hippocampus, Imipramine, Indoles, Male, Methylazoxymethanol Acetate, Mitosis, Neuronal Plasticity, Pyrrolidines, Stress, Psychological, Rats, Wistar, Prefrontal Cortex, Receptors, Corticotropin-Releasing Hormone, Rats, Cytostatic Agents, Neurogenesis, Antidiuretic Hormone Receptor Antagonists
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