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
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Items 601–605 of 605
Ivanov, I., Džinalija, N., Abe, Y., Alonso, P., Ameis, S. H., Arnold, P. D., Baker, J. T., Balachander, S., Banaj, N., Bargalló, N., et al. (2026) · Cortex · doi:10.1016/j.cortex.2026.08.015
Simard, S., & Mechawar, N. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03896-7
Naghizadeh, F., Niknazar, S., Dadseresht, A., Seidkhani, E., Alizadeh, R., & Arezo, N. (2026) · Research Square · doi:10.21203/rs.3.rs-11106755/v1
The HPA axis and GABA-Glutamate Systems as Potential Antidepressant Targets in Prostate Cancer
Sharpley, C. F. (2011) · The Open Prostate Cancer Journal · doi:10.2174/1876822901104010001 · Cited by 1
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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