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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
Cited by
Sorted by citations
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
Towards a glutamate hypothesis of depression
Sanacora, G., Treccani, G., & Popoli, M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.07.036 · Cited by 1,036
“An additional corollary, as evidenced by a number of studies, is that maladaptive plasticity in animal models can at least partly be reversed by therapeutic treatments, including antidepressants (Norrholm and Ouimet, 2001; Hajszan et al., 2009; Bessa et al., 2009).”
BackgroundThe chronic mild stress (CMS) model of depression: History, evaluation and usage
Willner, P. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.08.002 · Cited by 959
“These morphological changes are associated with a decrease in the volume of the hippocampus following CMS (Bessa et al., 2009; Delgado y Palacios et al., 2011), which is the major abnormality reported in structural imaging studies of patients with major depression (Campbell et al., 2004; Videbech…”
BackgroundResultInfluentialThe role of adult hippocampal neurogenesis in brain health and disease
Toda, T., Parylak, S. L., Linker, S. B., & Gage, F. H. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0036-2 · Cited by 719
MacQueen, G., & Frodl, T. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.80 · Cited by 665
Monoamine neurocircuitry in depression and strategies for new treatments
Hamon, M., & Blier, P. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.04.009 · Cited by 674
How do antidepressants work? New perspectives for refining future treatment approaches
Harmer, C. J., Duman, R. S., & Cowen, P. J. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30015-9 · Cited by 616
Brites, D., & Fernandes, A. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00476 · Cited by 599
“As the neurogenic process in the adult brain constitutes a new dimension of plasticity, ways to repair impairments in neuroplasticity may turn useful to treat depression (Bessa et al., 2009; Mateus-Pinheiro et al., 2013a,b).”
BackgroundPostpartum depression: Etiology, treatment and consequences for maternal care
Brummelte, S., & Galea, L. A. M. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.08.008 · Cited by 567
The neurobiology of depression and antidepressant action
Willner, P., Scheel-Krüger, J., & Belzung, C. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.12.007 · Cited by 519
“While neurogenesis appears to play a critical role in antidepressant action, blockade of neurogenesis, using X-irradiation or genetic tools, does not in itself induce a depressive phenotype (Santarelli et al., 2003; Airan et al., 2007; Bessa et al., 2009; Holick et al., 2008; Revest et al., 2009; Samuels and Hen, 2011…”
BackgroundInfluentialNeural Mechanisms of Stress Resilience and Vulnerability
Franklin, T. B., Saab, B. J., & Mansuy, I. M. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.016 · Cited by 500
Antidepressants recruit new neurons to improve stress response regulation
Surget, A., Tanti, A., Leonardo, E. D., Laugeray, A., Rainer, Q., Touma, C., Palme, R., Griebel, G., Ibarguen-Vargas, Y., Hen, R., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.48 · Cited by 471
Sex differences in depression: Insights from clinical and preclinical studies
Eid, R. S., Gobinath, A. R., & Galea, L. A. M. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.01.006 · Cited by 481
“In our own model of PPD using high levels of CORT during the postpartum, we have consistently seen that SSRIs (paroxetine and fluoxetine) improve CORT-induced maternal care deficits (Gobinath et al., 2018; Overgaard et al., 2018; Workman et al., 2016), but not immobility in the FST (Workman et al., 2016; Gobinath et a…”
BackgroundInfluentialKubera, M., Obuchowicz, E., Goehler, L., Brzeszcz, J., & Maes, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.08.026 · Cited by 443
Treatment resistant depression: A multi-scale, systems biology approach
Akil, H., Gordon, J. A., Hen, R., Javitch, J. A., Mayberg, H. S., McEwen, B. S., Meaney, M. J., & Nestler, E. J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.08.019 · Cited by 463
“We and others showed that hippocampal neurogenesis is necessary (Santarelli et al., 2003) and sufficient (Hill et al., 2015) for some but not all of the behavioral effects of several classes of antidepressants (David et al., 2009; Bessa et al., 2009).”
BackgroundAntidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor
Anacker, C., Zunszain, P. A., Cattaneo, A., Carvalho, L. A., Garabedian, M. J., Thuret, S., Price, J., & Pariante, C. M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.26 · Cited by 435
Abdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-053013-062946 · Cited by 422
Joëls, M., Sarabdjitsingh, R. A., & Karst, H. (2012) · Pharmacological Reviews · doi:10.1124/pr.112.005892 · Cited by 445
“, 2010), which may or may not be linked to dendritic remodeling in the dentate gyrus (Bessa et al., 2009).”
BackgroundHinwood, M., Morandini, J., Day, T. A., & Walker, F. R. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr229 · Cited by 420
“The ability of psychological stress reduce the capacity of working memory in the rat has been well described (Arnsten and Goldman-Rakic 1998; Cerqueira et al. 2007; Bessa et al. 2009; Qin et al. 2009).”
BackgroundNeurobiology of chronic mild stress: parallels to major depression
Hill, M. N., Hellemans, K. G. C., Verma, P., Gorzalka, B. B., & Weinberg, J. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.001 · Cited by 420
“…Sandi et al., 2008; Li et al., 2007, 2008, 006; Kong et al., 2009; Zhou et al., 2007; Alonso et al., 2004; Liu t al., 2008; Silva et al., 2008; Bessa et al., 2009; Jayatissa et al., 2/cage ↑ pERK1/2 levels (VTA) Iniguez et al. (2010) 2/cage ↑ RGS4 mRNA (LC) Ni et al. (1999) 2009; Guo et al.,…”
Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression
Allen, J., Romay-Tallón, R., Brymer, K. J., Caruncho, H. J., & Kalynchuk, L. E. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00386 · Cited by 362
“Instead, some data suggest that depression and the therapeutic actions of antidepressants may be more related to alterations in dendritic complexity and neuronal remodeling than cell number per se (Bessa et al., 2009; Lussier et al., 2013).”
BackgroundBrain-derived neurotrophic factor in mood disorders and antidepressant treatments
Castrén, E., & Kojima, M. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.010 · Cited by 337
“Second, antidepressants increase axon elongation and dendritic sprouting (Vaidya et al., 1999; Wang et al., 2008; Bessa et al., 2009; Chen et al., 2011) as well as expression of plasticity-related proteins (Sairanen et al., 2007).”
Neuroplastic changes in depression: A role for the immune system
Eyre, H., & Baune, B. T. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.019 · Cited by 319
Chronic stress and glucocorticoids: From neuronal plasticity to neurodegeneration
Vyas, S., Rodrigues, A. J., Silva, J. M., Tronche, F., Almeida, O. F. X., Sousa, N., & Sotiropoulos, I. (2016) · Neural Plasticity · doi:10.1155/2016/6391686 · Cited by 297
“This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.”
BackgroundSelf-citationKetamine Treatment and Global Brain Connectivity in Major Depression
Abdallah, C. G., Averill, L. A., Collins, K. A., Geha, P., Schwartz, J., Averill, C., DeWilde, K. E., Wong, E., Anticevic, A., Tang, C. Y., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.186 · Cited by 300
Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
Crippa, J. A., Guimarães, F. S., Campos, A. C., & Zuardi, A. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02009 · Cited by 308
Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression
Levy, M. J. F., Boulle, F., Steinbusch, H. W., van den Hove, D. L. A., Kenis, G., & Lanfumey, L. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4950-4 · Cited by 308
Depression during pregnancy and postpartum: Contribution of stress and ovarian hormones
Brummelte, S., & Galea, L. A. M. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.09.006 · Cited by 307
Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal
Hanson, N. D., Owens, M. J., & Nemeroff, C. B. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.220 · Cited by 311
Micheli, L., Ceccarelli, M., D’Andrea, G., & Tirone, F. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.09.002 · Cited by 288
Regulation of hippocampal H3 histone methylation by acute and chronic stress
Hunter, R. G., McCarthy, K. J., Milne, T. A., Pfaff, D. W., & McEwen, B. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911143106 · Cited by 290
Stress, anxiety, and dendritic spines: What are the connections?
Leuner, B., & Shors, T. J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.021 · Cited by 284
Neuronal plasticity and neurotrophic factors in drug responses
Castrén, E., & Antila, H. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.61 · Cited by 284
Fuchikami, M., Thomas, A., Liu, R., Wohleb, E. S., Land, B. B., DiLeone, R. J., Aghajanian, G. K., & Duman, R. S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414728112 · Cited by 265
“Neuropsychopharmacology 30(12):2275–2282.”
BackgroundSpine synapse remodeling in the pathophysiology and treatment of depression
Duman, C. H., & Duman, R. S. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.022 · Cited by 257
Depression in neurodegenerative diseases: Common mechanisms and current treatment options
Galts, C., Bettio, L. E. B., Jewett, D. C., Yang, C. C., Brocardo, P. S., Rodrigues, A. L. S., Thacker, J. S., & Gil‐Mohapel, J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.04.002 · Cited by 276
Review: adult neurogenesis contributes to hippocampal plasticity
Toda, T., & Gage, F. H. (2017) · Cell and Tissue Research · doi:10.1007/s00441-017-2735-4 · Cited by 279
“…most studies have shown that the ablation of adult-born neurons does not affect the baseline levels of anxiety (David et al. 2009; Kitamura et al. 2009; Saxe et al. 2006), suggesting that adult neurogenesis is important for the stress response but not in every case (Bessa et al. 2009).”
BackgroundNeuronal plasticity and antidepressant actions
Castrén, E., & Hen, R. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.12.010 · Cited by 243
Sex differences in the antidepressant-like effects of ketamine
Carrier, N., & Kabbaj, M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.12.009 · Cited by 251
“, 2009; Shansky and Morrison, 2009) effects that are reversed by classical antidepressant treatments (Bessa et al., 2009; Hajszan et al., 2009; Norrholm and Ouimet, 2001; Wood et al., 2004) as well as by acute ketamine treatment (Li et al.”
BackgroundDuman, R. S. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.1/rduman · Cited by 249
Lehmann, M. L., & Herkenham, M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0577-11.2011 · Cited by 234
“, 2001) or stressinduced IL dendritic retraction produces deficits in fear extinction (Bessa et al., 2009), leading to anxiety disorders.”
BackgroundPetrik, D., Lagace, D. C., & Eisch, A. J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.09.003 · Cited by 241
“As shown in Table 1, there are currently 21 publications that have examined the depression- and anxiety-related behavioral consequences of decreasing neurogenesis in laboratory animals (Airan et al., 2007; Bessa et al., 2009; David et al., 2009; Fuss et al., 2010a; Holick et al., 2008; Jayatissa et al., 2009; Lagace e…”
BackgroundMethodInfluentialGalea, L. A. M., Wainwright, S. R., Roes, M., Duarte‐Guterman, P., Chow, C., & Hamson, D. K. (2013) · Journal of Neuroendocrinology · doi:10.1111/jne.12070 · Cited by 247
Magariños, A. M., Li, C. J., Gal Toth, J., Bath, K. G., Jing, D., Lee, F. S., & McEwen, B. S. (2011) · Hippocampus · doi:10.1002/hipo.20744 · Cited by 232
Zhu, X.-H., Yan, H., Zhang, J., Qu, H.-D., Qiu, X., Chen, L., Li, S.-J., Cao, X., Bean, J. C., Chen, L. H., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.6414-09.2010 · Cited by 229
“Exposure to CMS increased the latency to feed (F(3,24) 7.1; p 0.01; post hoc analysis, p 0.001 control vs saline group), an effect that was partially reversed by fluoxetine ( p 0.01 vs saline group), in agreement with previous reports (Bessa et al., 2009).”
InfluentialTanti, A., & Belzung, C. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.08.017 · Cited by 226
Mathews, D. C., Henter, I. D., & Zarate, C. A. (2012) · Drugs · doi:10.2165/11633130-000000000-00000 · Cited by 220
“Such changes would effectively limit the number of exposed glutamate receptors and as a result, drugs thought to reduce glutamatergic neurotransmission may prevent dendritic retraction and protect brain synapses.([46,51]) Interestingly, glutamatergic neurotransmission may further be altered at the genetic level, where…”
BackgroundRole of adult hippocampal neurogenesis in stress resilience
Levone, B. R., Cryan, J. F., & O'Leary, O. F. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.11.003 · Cited by 218
“However, it is also important to note that negative findings have also been reported (Surget et al., 2011; Bessa et al., 2009; David et al., 2009).”
BackgroundResultInfluentialThe impact of chronic stress on the rat brain lipidome
Oliveira, T. G., Chan, R., Bravo, F. V., Miranda, A. M., Caridade-Silva, R., Zhou, B., Marques, F., Pinto, V., Cerqueira, J., Paolo, G. D., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.14 · Cited by 218
Self-citationDuman, R. S. (2014) · Depression and Anxiety · doi:10.1002/da.22227 · Cited by 213
Monteiro, S., Roque, S., de Sá-Calçada, D., Sousa, N., Correia-Neves, M., & Cerqueira, J. J. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00006 · Cited by 216
“Although not often used in mice, CUS protocols are widely used in rats and were shown to be highly effective in inducing a stress-related phenotype (6, 11, 12, 36).”
MethodSelf-citationDuman, R. S. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.3/rsduman · Cited by 210
Brummelte, S., & Galea, L. A. M. (2010) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.07.012 · Cited by 216
“This dissociation is consistent with other studies (Bessa et al., 2008), including another animal model of postpartum depression from our laboratory (Green and Galea, 2008) but inconsistent with a number of other studies showing a link between depressive like behavior in the forced swim test and hippocampal cell proli…”
Garza, J. C., Guo, M., Zhang, W., & Lu, X.-Y. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.161 · Cited by 209
Alboni, S., van Dijk, R. M., Poggini, S., Milior, G., Perrotta, M., Drenth, T., Brunello, N., Wolfer, D. P., Limatola, C., Amrein, I., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2015.142 · Cited by 207
Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms
Mahmoud, R., Wainwright, S. R., & Galea, L. A. M. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.03.002 · Cited by 208
“…reviewed above, that chronic stress decreases hippocampal neurogenesis in animal models of depression (Gould et al., 1997; Santarelli et al., 2003; Bessa et al., 2009), but that antidepressant drugs can both prevent (Czeh et al., 2001; Alonso et al., 2004) and reverse (Malberg and Duman, 2003;…”
BackgroundInfluentialActivating newborn neurons suppresses depression and anxiety-like behaviors
Tunc‐Ozcan, E., Peng, C., Zhu, Y., Dunlop, S. R., Contractor, A., & Kessler, J. A. (2019) · Nature Communications · doi:10.1038/s41467-019-11641-8 · Cited by 203
“Therefore, increased neurogenesis may be necessary for the effects of anti-depressants, although this remains controversial because of the lack of speci fi city of the techniques used to target newborn neurons 17 – 19 .”
Salvadore, G., Nugent, A. C., Lemaître, H., Luckenbaugh, D. A., Tinsley, R., Cannon, D. M., Neumeister, A., Zarate, C. A., & Drevets, W. C. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.11.011 · Cited by 195
“However, most of the patients (79%) enrolled in this study were receiving antidepressant drugs at the time of scanning, potentially limiting the interpretability and generalizability of the results, particularly given previous evidence that these agents upregulate neurotrophin expression (Duman and Monteggia, 2006), c…”
Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine
Deyama, S., & Duman, R. S. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.172837 · Cited by 186
“Chronic fluoxetine or imipramine treatment also reverse the spine deficits in hippocampal and cortical regions caused by CUS exposure (Bessa et al., 2009); chronic fluoxetine treatment has been reported to reverse depression-like behavior and the reduction in dendritic length and spine density in CA1 pyramidal neurons…”
BackgroundWang, Y.-S., Shen, C., & Jiang, J. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104520 · Cited by 189
Adult Neurogenesis and Mental Illness
Schoenfeld, T. J., & Cameron, H. A. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.230 · Cited by 192
“Bessa et al (2009) found increased latency to eat under similar conditions; however, the dose of MAM used to inhibit neurogenesis may decrease motivation to eat independent of its effects on neurogenesis (Dupret et al, 2005; Shors et al, 2001).”
BackgroundMethodHuang, Y., Coupland, N. J., Lebel, R. M., Carter, R., Seres, P., Wilman, A. H., & Malykhin, N. V. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.01.005 · Cited by 179
“This is in agreement with previous animal studies that found that antidepressant treatment can prevent CA and DG spine loss (54–56), CA and DG dendritic retraction (54,57), and astrocyte loss (58).”
ResultEpigenetic mechanisms of major depression: Targeting neuronal plasticity
Uchida, S., Yamagata, H., Seki, T., & Watanabe, Y. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12621 · Cited by 181
Guardiola‐Lemaitre, B., De Bodinat, C., Delagrange, P., Millan, M. J., Munoz, C., & Mocaër, E. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12720 · Cited by 182
“These findings, which may be related to regulation of microtubule dynamics and/or dendritic remodelling, as also seen with fluoxetine (Bessa et al., 2009), are in agreement with the findings that (sub)chronic administration of different classes of antidepressants (imipramine, desipramine, fluvoxamine) can affect MAP-2…”
ResultHippocampal neuroplasticity in major depressive disorder
Malykhin, N. V., & Coupland, N. J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.04.047 · Cited by 190
Campos, A. C., Fogaça, M. V., Scarante, F. F., Joca, S. R. L., Sales, A. J., Gomes, F. V., Sonego, A. B., Rodrigues, N. S., Galve-Roperh, I., & Guimarães, F. S. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00269 · Cited by 175
“Repeated antidepressant treatment also prevents stress-induced hippocampal dendritic atrophy (Bessa et al., 2009) and facilitates adult hippocampal neurogenesis in rodents (Malberg et al., 2000; Santarelli et al., 2003).”
BackgroundLee, T., Jarome, T., Li, S.-J., Kim, J. J., & Helmstetter, F. J. (2009) · NeuroReport · doi:10.1097/wnr.0b013e328332bb09 · Cited by 173
Musazzi, L., Treccani, G., Mallei, A., & Popoli, M. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.009 · Cited by 178
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
“antidepressant treatment restores dendritic atrophy induced by chronic stress in rodents [235].”
BackgroundYau, S.-Y., Lau, B. W.-M., Tong, J.-B., Wong, R., Ching, Y.-P., Qiu, G., Tang, S.-W., Lee, T. M. C., & So, K.-F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024263 · Cited by 169
“It has been reported in a rat model using 2-week exposure to unpredictable chronic stress that antidepressants improved depressive behaviours that is neurogenesis independent, but is associated with dendritic remodeling in the prefrontal cortex and hippocampus”
BackgroundGlutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments
Kadriu, B., Musazzi, L., Henter, I. D., Graves, M., Popoli, M., & Zarate, C. A. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyy094 · Cited by 165
Dellarole, A., Morton, P. D., Brambilla, R., Walters, W. M., Summers, S. H., Bernardes, D., Grilli, M., & Bethea, J. R. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.04.003 · Cited by 170
“, 2011), other authors demonstrated that re-establishment of neuronal plasticity, rather than neurogenesis, is the basis for the restoration of behavioral homeostasis by antidepressants (Bessa et al., 2009).”
Wainwright, S. R., & Galea, L. A. M. (2013) · Neural Plasticity · doi:10.1155/2013/805497 · Cited by 169
Cavalleri, L., Merlo Pich, E., Millan, M. J., Chiamulera, C., Kunath, T., Spano, P. F., & Collo, G. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.241 · Cited by 156
“BDNF-TrkB signaling has been extensively studied as a potential substrate for the influence of antidepressants on functional(65) and structural plasticity.(24,26,66) Increased BDNF synthesis and release in rodent frontocortical/hippocampal circuits were observed after acute exposure to either ketamine(5,14,17) or AMPA…”
BackgroundClinically Significant Drug Interactions with Newer Antidepressants
Spina, E., Trifirò, G., & Caraci, F. (2011) · CNS Drugs · doi:10.2165/11594710-000000000-00000 · Cited by 164
Disconnection and reconnection: The morphological basis of (mal)adaptation to stress
Sousa, N., & Almeida, O. F. X. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.08.006 · Cited by 159
Self-citationPharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy
Mnie‐Filali, O., Faure, C., Lambás‐Señas, L., Mansari, M. E., Belblidia, H., Gondard, E., Etiévant, A., Scarna, H., Didier, A., Bérod, A., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.13 · Cited by 161
“As it has been recently proposed (Bessa et al., 2009), neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus, rather than neurogenesis itself, could be responsible for the latter behavioural phenotypes of 5-HT 7 mutant mice.”
BackgroundRemodeling of axo-spinous synapses in the pathophysiology and treatment of depression
Licznerski, P., & Duman, R. S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.09.057 · Cited by 157
“Chronic administration of fluoxetine or the tricylic antidepressant imipramine is reported to rescue dendrite atrophy and spine loss in hippocampal CA3 and medial PFC layer II/III pyramidal neurons caused by chronic stress (Bessa et al., 2009).”
Depression, stress, epilepsy and adult neurogenesis
Danzer, S. C. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.05.023 · Cited by 157
“Instead, enhanced neuronal plasticity may be important (Wang et al., 2008; Bessa et al., 2009).”
BackgroundBranchi, I. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.08.011 · Cited by 156
“This suggests that an intimate relationship between these two phenomena is likely to exist (Pittenger and Duman, 2008; Bessa et al., 2009).”
BackgroundWager‐Smith, K., & Markou, A. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.09.010 · Cited by 153
“It should be noted, however, that a minority of studies did not find any neurogenesis-dependence to antidepressant effects on behavior (Bessa et al. 2009, Holick et al. 2008), and the dependence appears to vary in behavioral endpoint-specific (David et al. 2009), and antidepressant-specific (Surget…”
BackgroundInfluentialSustained remission from depressive-like behavior depends on hippocampal neurogenesis
Mateus-Pinheiro, A., Pinto, L., Bessa, J. M., Morais, M., Alves, N. D., Monteiro, S., Patrício, P., Almeida, O. F. X., & Sousa, N. (2013) · Translational Psychiatry · doi:10.1038/tp.2012.141 · Cited by 149
“Pilot studies showed that MAM did not adversely influence general health parameters, such as locomotor activity (ambulation in an open field, swimming speed in a water maze) and fur quality.(8,16,17) Here, we found no significant alterations induced by MAM in appetite drive (Supplementary Figure S1), in swimming perfo…”
BackgroundMethodInfluentialSelf-citationGABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response
Gunn, B. G., Cunningham, L., Mitchell, S. G., Swinny, J. D., Lambert, J. J., & Belelli, D. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.06.001 · Cited by 149
“However, it should be noted that the therapeutic actions of certain antidepressant compounds have been reported to occur in a neurogenesis-independent manner (Surget et al., 2008; Bessa et al., 2009).”
Endocrine substrates of cognitive and affective changes during pregnancy and postpartum.
Workman, J. L., Barha, C. K., & Galea, L. A. M. (2011) · Behavioral Neuroscience · doi:10.1037/a0025538 · Cited by 159
Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine
Wohleb, E. S., Gerhard, D. M., Thomas, A., & Duman, R. S. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160309114549 · Cited by 151
“Chronic administration of the selective serotonin-reuptake inhibitor (SSRI) fluoxetine is able to increase spine density [48] and block the stress-induced atrophy of dendrites and spines following chronic stressors [49, 50].”
Tau protein is essential for stress-induced brain pathology
Lopes, S., Vaz‐Silva, J., Pinto, V., Dalla, C., Kokras, N., Bedenk, B. T., Mack, N., Czisch, M., Almeida, O. F. X., Sousa, N., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600953113 · Cited by 147
“Clinical and preclinical studies have shown that prolonged exposure to stressful conditions impairs structural and functional plasticity of the hippocampal formation related to stress-driven cognitive and mood deficits (7, 8, 23).”
BackgroundMethodResultInfluentialSelf-citationLi, W., Ali, T., Zheng, C., Liu, Z., He, K., Shah, F. A., Ren, Q., Rahman, S. U., Li, N., Yu, Z., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02091-5 · Cited by 148
“Furthermore, previous results studying the molecular and cellular mechanisms of fluoxetine show ambiguous results of BDNF level and neurogenesis [78, 79], [80], [81–85], demanding further investigations to delineate the pharmacological basis of fluoxetine.”
ResultChronic mild stress paradigm as a rat model of depression: facts, artifacts, and future perspectives
Strekalova, T. V., Liu, Y., Kiselev, D., Khairuddin, S., Chiu, J. L. Y., Lam, J., Chan, Y., Pavlov, D., Proshin, A. T., Lesch, K., et al. (2022) · Psychopharmacology · doi:10.1007/s00213-021-05982-w · Cited by 152
Neuronal correlates of depression
Chaudhury, D., Liu, H., & Han, M. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2044-6 · Cited by 150
Phoumthipphavong, V., Barthas, F., Hassett, S., & Kwan, A. C. (2016) · eneuro · doi:10.1523/eneuro.0133-15.2016 · Cited by 132
“Therefore, our results and studies in the field (Bessa et al., 2009; Li et al., 2010, 2011; Voleti et al., 2013) support a structural basis for antidepressant actions that may generalize beyond specific frontal cortical regions or pharmacological agents.”
BackgroundResultInfluentialDysfunctional hippocampal activity affects emotion and cognition in mood disorders
Femenía, T., Gómez-Galán, M., Lindskog, M., & Magara, S. (2012) · Brain Research · doi:10.1016/j.brainres.2012.03.053 · Cited by 143
Morley‐Fletcher, S., Mairesse, J., Soumier, A., Banasr, M., Fagioli, F., Gabriel, C., Mocaër, E., Daszuta, A., McEwen, B. S., Nicoletti, F., et al. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2280-x · Cited by 149
“…induced by chronic corticosterone treatment, only some “therapeutic effects” of fluoxetine are neurogenesisdependent (David et al. 2009), and there is also evidence that antidepressants retain their “therapeutic” efficacy when neurogenesis is blocked by a cytostatic drug (Bessa et al. 2009).”
McKernan, D. P., Dinan, T. G., & Cryan, J. F. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.04.006 · Cited by 139
“Besides neurogenesis, it has also been shown that antidepressants play a key role in neuronal remodelling (Bessa et al., 2008) and synaptic plasticity (reviewed in Castren, 2004).”
BackgroundBatalha, V. L., Pego, J. M., Fontinha, B. M., Costenla, A. R., Valadas, J. S., Baqi, Y., Radjainia, H., Müller, C. E., Sebastião, A. M., & Lopes, L. V. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.8 · Cited by 136
Ampuero, E., Rubio, F. J., Falcon, R., Sandoval, M., Diaz-Veliz, G., Gonzalez, R. E., Earle, N., Dagnino-Subiabre, A., Aboitiz, F., Orrego, F., et al. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.04.035 · Cited by 132
Dwyer, J. M., & Duman, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.011 · Cited by 139
“Chronic treatment with typical antidepressants can also reverse the neuronal atrophy and decrease in spine density in the hippocampus and PFC produced by chronic stress (57).”
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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