Alterations in 5-HT 1B Receptor Function by p11 in Depression-Like States
Abstract
The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT 1B ) receptor] interacts with p11. p11 increases localization of 5-HT 1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT 1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT 1B receptor agonists and reduced behavioral reactions to an antidepressant.
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The genes chosen for expression analysis have all recently been implicated in antidepressant drug action and neurogenesis.
“These genes were chosen because they have all recently been implicated in antidepressant drug action and neurogenesis.35, 36, 37, 38, 39, 12, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49”
From Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor (2011) · cites this paper as [42]
p11 and ß-arrestin-2 have been implicated in antidepressant effects on neurogenesis in vivo.
“p11 and ß-arrestin-2, which have both recently been implicated in the antidepressant effects on neurogenesis in vivo.12, 40, 42, 43”
From Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor (2011) · cites this paper as [42]
p11 deficiency, p11 reductions in NAc, or p11 knockout in NAc ChIs is sufficient to reduce sucrose preference and increase forced-swim immobility.
“Mice lacking p11 [162], p11 reductions in NAc [163], or p11 knockout in NAc ChIs [158] is sufficient to reduce sucrose preference and increase forced-swim immobility (Fig. 2, top).”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [162]
Cites
A molecular and cellular theory of depression
Duman, R. S. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830190015002 · Cited by 2,129 · see citing works
The cellular neurobiology of depression
Manji, H. K., Drevets, W. C., & Charney, D. S. (2001) · Nature Medicine · doi:10.1038/87865 · Cited by 1,182 · see citing works
Enhanced Aggressive Behavior in Mice Lacking 5-HT 1B Receptor
Saudou, F., Amara, D. A., Dierich, A., LeMeur, M., Ramboz, S., Ségu, L., Buhot, M.-C., & Hen, R. (1994) · Science · doi:10.1126/science.8091214 · Cited by 839 · see citing works
Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type
Donato, R. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(99)00058-0 · Cited by 679 · see citing works
van de Graaf, S. F. J., Hoenderop, J. G. J., Gkika, D., Lamers, D., Prenen, J., Rescher, U., Gerke, V., Staub, O., Nilius, B., & Bindels, R. J. M. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg162 · Cited by 285 · see citing works
Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice
Gingrich, J. A., & Hen, R. (2001) · Psychopharmacology · doi:10.1007/s002130000573 · Cited by 265 · see citing works
Yacoubi, M. E., Bouali, S., Popa, D., Naudon, L., Leroux‐Nicollet, I., Hamon, M., Costentin, J., Adrien, J., & Vaugeois, J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1034823100 · Cited by 263 · see citing works
Self-citationGPCR interacting proteins (GIP)
Bockaert, J., Fagni, L., Dumuis, A., & Marin, P. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.06.004 · Cited by 262 · see citing works
Annexin II light chain regulates sensory neuron-specific sodium channel expression
Okuse, K., Malik‐Hall, M., Baker, M. D., Poon, W.-Y. L., Kong, H., Chao, M. V., & Wood, J. N. (2002) · Nature · doi:10.1038/nature00781 · Cited by 257 · see citing works
Deora, A. B., Kreitzer, G. E., Jacovina, A. T., & Hajjar, K. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408078200 · Cited by 233 · see citing works
Maroteaux, L., Saudou, F., Amlaiky, N., Boschert, U., Plassat, J., & Hen, R. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.3020 · Cited by 219 · see citing works
p11, an annexin II subunit, an auxiliary protein associated with the background K+ channel, TASK‐1
Girard, C. A. J., Tinel, N., Terrenoire, C., Romey, G., Lazdunski, M., & Borsotto, M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf469 · Cited by 148 · see citing works
Moret, C., & Briley, M. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00581-1 · Cited by 118 · see citing works
Regulation of Central Synaptic Transmission by 5-HT1B Auto- and Heteroreceptors
Morikawa, H., Manzoni, O. J., Crabbe, J. C., & Williams, J. T. (2000) · Molecular Pharmacology · doi:10.1124/mol.58.6.1271 · Cited by 92 · see citing works
Schlicker, E., Werner, U., Hamon, M., GOZLAN, H., Nickel, B., Szelényi, L., & Göthert, M. (1992) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1992.tb09047.x · Cited by 75 · see citing works
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The molecular neurobiology of depression
Krishnan, V., & Nestler, E. J. (2008) · Nature · doi:10.1038/nature07455 · Cited by 2,889 · see citing works
Spatio-temporal transcriptome of the human brain
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A. M. M., Pletikos, M., Meyer, K. A., Sedmak, G., et al. (2011) · Nature · doi:10.1038/nature10523 · Cited by 2,084 · see citing works
Belmaker, R. H., & Agam, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra073096 · Cited by 2,166 · see citing works
Physical Activity and Mental Health: Current Concepts
Paluska, S. A., & Schwenk, T. L. (2000) · Sports Medicine · doi:10.2165/00007256-200029030-00003 · Cited by 1,722 · see citing works
New insights into BDNF function in depression and anxiety
Martinowich, K., Manji, H., & Lu, B. (2007) · Nature Neuroscience · doi:10.1038/nn1971 · Cited by 1,221 · see citing works
The GABAergic deficit hypothesis of major depressive disorder
Luscher, B., Shen, Q., & Sahir, N. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.120 · Cited by 934 · see citing works
Pathogenesis of depression: Insights from human and rodent studies
Ménard, C., Hodes, G. E., & Russo, S. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.053 · Cited by 593 · see citing works
Animal Models of Depression: Molecular Perspectives
Krishnan, V., & Nestler, E. J. (2011) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2010_108 · Cited by 528 · see citing works
The nucleus accumbens: a comprehensive review
Salgado, S., & Kaplitt, M. G. (2015) · Stereotactic and Functional Neurosurgery · doi:10.1159/000368279 · Cited by 489 · see citing works
Antidepressants 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 · see citing works
Hashimoto, K. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12902 · Cited by 335 · see citing works
Serotonin receptors involved in antidepressant effects
Artigas, F. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.09.006 · Cited by 311 · see citing works
Klempan, T. A., Sequeira, A., Canetti, L., Lalovic, A., Ernst, C., ffrench-Mullen, J., & Turecki, G. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002110 · Cited by 294 · see citing works
Warner-Schmidt, J. L., Vanover, K. E., Chen, E. Y., Marshall, J. J., & Greengard, P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104836108 · Cited by 291 · see citing works
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Vialou, V., Feng, J., Robison, A. J., & Nestler, E. J. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134540 · Cited by 277 · see citing works
The role of the innate immune system in psychiatric disorders
Jones, K. A., & Thomsen, C. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.10.002 · Cited by 274 · see citing works
Hu, H. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014106 · Cited by 253 · see citing works
Wipfli, B., Landers, D., Nagoshi, C., & Ringenbach, S. (2011) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/j.1600-0838.2009.01049.x · Cited by 242 · see citing works
Cellular and molecular basis for stress-induced depression
Seo, J.-S., Wei, J., Qin, L., Kim, Y., Yan, Z., & Greengard, P. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.118 · Cited by 235 · see citing works
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MICHELSEN, K., PRICKAERTS, J., & STEINBUSCH, H. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00912-6 · Cited by 196 · see citing works
Guidotti, G., Calabrese, F., Anacker, C., Racagni, G., Pariante, C. M., & Riva, M. A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.225 · Cited by 200 · see citing works
Cai, X., Kallarackal, A. J., Kvarta, M. D., Goluskin, S., Gaylor, K., Bailey, A. M., Lee, H.-K., Huganir, R. L., & Thompson, S. M. (2013) · Nature Neuroscience · doi:10.1038/nn.3355 · Cited by 180 · see citing works
Epigenetic Signaling in Psychiatric Disorders
Peña, C. J., Bagot, R. C., Labonté, B., & Nestler, E. J. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.03.016 · Cited by 163 · see citing works
Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior
Warner-Schmidt, J. L., Schmidt, E. F., Marshall, J. J., Rubin, A. J., Arango-Lievano, M., Kaplitt, M. G., Ibañez-Tallon, I., Heintz, N., & Greengard, P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209293109 · Cited by 163 · see citing works
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Neuropathology of suicide: Recent findings and future directions
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Melas, P. A., Rogdaki, M., Lennartsson, A., Björk, K., Qi, H., Witasp, A., Werme, M., Wegener, G., Mathé, A. A., Svenningsson, P., et al. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000940 · Cited by 157 · see citing works
Self-citationSerum markers support disease-specific glial pathology in major depression
Schroeter, M. L., Abdul-Khaliq, H., Krebs, M., Diefenbacher, A., & Blasig, I. E. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.03.005 · Cited by 152 · see citing works
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Alexander, B., Warner-Schmidt, J., Eriksson, T. M., Tamminga, C., Arango-Lievano, M., Ghose, S., Vernov, M., Stavarache, M., Musatov, S., Flajolet, M., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001079 · Cited by 140 · see citing works
Self-citationDepression pathogenesis and treatment: what can we learn from blood mRNA expression?
Hepgul, N., Cattaneo, A., Zunszain, P. A., & Pariante, C. M. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-28 · Cited by 127 · see citing works
HCN2 Channels in Cholinergic Interneurons of Nucleus Accumbens Shell Regulate Depressive Behaviors
Cheng, J., Umschweif, G., Leung, J., Sagi, Y., & Greengard, P. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.018 · Cited by 110 · see citing works
Self-citationMechanisms of antidepressant resistance
El-Hage, W., Leman, S., Camus, V., & Belzung, C. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00146 · Cited by 111 · see citing works
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Egeland, M., Warner-Schmidt, J., Greengard, P., & Svenningsson, P. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.024 · Cited by 94 · see citing works
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Chen, G., Henter, I. D., & Manji, H. K. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.3 · Cited by 95 · see citing works
Yamanaka, H., Yokoyama, C., Mizuma, H., Kurai, S., Finnema, S. J., Halldin, C., Doi, H., & Onoe, H. (2014) · Translational Psychiatry · doi:10.1038/tp.2013.112 · Cited by 84 · see citing works
GSK3β: a master player in depressive disorder pathogenesis and treatment responsiveness
Duda, P., Hajka, D., Wójcicka, O., Rakus, D., & Gizak, A. (2020) · Cells · doi:10.3390/cells9030727 · Cited by 84 · see citing works
Martín-Hernández, D., Caso, J. R., Javier Meana, J., Callado, L. F., Madrigal, J. L. M., García-Bueno, B., & Leza, J. C. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1294-2 · Cited by 80 · see citing works
Molecular and cell signaling targets for PTSD pathophysiology and pharmacotherapy
Hauger, R. L., Olivares-Reyes, J. A., Dautzenberg, F. M., Lohr, J. B., Braun, S., & Oakley, R. H. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.11.007 · Cited by 71 · see citing works
Hahn, A., Haeusler, D., Kraus, C., Höflich, A. S., Kranz, G. S., Baldinger, P., Savli, M., Mitterhauser, M., Wadsak, W., Karanikas, G., et al. (2014) · Human Brain Mapping · doi:10.1002/hbm.22442 · Cited by 66 · see citing works
Reverse translational strategies for developing animal models of bipolar disorder
Malkesman, O., Austin, D. R., Chen, G., & Manji, H. K. (2009) · Disease Models & Mechanisms · doi:10.1242/dmm.001628 · Cited by 70 · see citing works
Neurophysiological mechanisms of electroconvulsive therapy for depression
Kato, N. (2009) · Neuroscience Research · doi:10.1016/j.neures.2009.01.014 · Cited by 65 · see citing works
Towards translational rodent models of depression
O’Leary, O. F., & Cryan, J. F. (2013) · Cell and Tissue Research · doi:10.1007/s00441-013-1587-9 · Cited by 60 · see citing works
Bidirectional regulation of emotional memory by 5-HT1B receptors involves hippocampal p11
Eriksson, T. M., Alvarsson, A., Stan, T. L., Zhang, X., Hascup, K. N., Hascup, E. R., Kehr, J., Gerhardt, G. A., Warner-Schmidt, J., Arango-Lievano, M., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.130 · Cited by 45 · see citing works
Bortolozzi, A., Manashirov, S., Chen, A., & Artigas, F. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107873 · Cited by 37 · see citing works
Molecular and Cellular Mechanisms of Antidepressant Action
Sharp, T. (2012) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2012_216 · Cited by 36 · see citing works
Park, S. W., Nhu, L. H., Cho, H. Y., Seo, M. K., Lee, C. H., Ly, N. N., Choi, C. M., Lee, B. J., Kim, G.-M., Seol, W., et al. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.02.010 · Cited by 33 · see citing works
A Role for Serotonin in Modulating Opposing Drive and Brake Circuits of Impulsivity
Desrochers, S. S., Spring, M. G., & Nautiyal, K. M. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.791749 · Cited by 29 · see citing works
Shiotani, A., Kusunoki, H., Kimura, Y., Ishii, M., Imamura, H., Tarumi, K.-I., Manabe, N., Kamada, T., Hata, J., & Haruma, K. (2013) · Digestive Diseases and Sciences · doi:10.1007/s10620-013-2677-y · Cited by 26 · 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
Mendez‐David, I., David, D. J., Deloménie, C., Tritschler, L., Beaulieu, J., Colle, R., Corruble, E., Gardier, A. M., & Hen, R. (2023) · Hippocampus · doi:10.1002/hipo.23568 · Cited by 15 · see citing works
Wang, T., Li, L., Yue, Y., Liu, X., Chen, S., Shen, T., Xu, Z., & Yuan, Y. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.06.042 · Cited by 10 · see citing works
- Authors
- Svenningsson, P., Chergui, K., Rachleff, I., Flajolet, M., Zhang, X., Yacoubi, M. E., Vaugeois, J.-M., Nomikos, G. G., & Greengard, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Greengard, Paul
- ORCID
- Venue
- Science
- Published
- 2006-01-06
- Volume
- 311
- Issue
- 5757
- Pages
- 77-80
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1987194328
- Cited by
- 572
- References
- 15
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 21 · 2023: 13 · 2022: 19 · 2021: 23 · 2020: 24 · 2019: 32 · 2018: 18 · 2017: 23 · 2016: 28 · 2015: 24 · 2014: 30 · 2013: 34 · 2012: 36
- FWCI
- 27.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of Mental Health (MH40899, P01MH040899)
- National Institute on Drug Abuse (DA10044, P01DA010044)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- p11, 5-HT1B receptor, serotonin signaling, depression, antidepressants, electroconvulsive therapy, receptor trafficking, cell surface localization, depression-like behavior
- MeSH terms
- S100 Calcium Binding Protein A10, Adult, Aged, Animals, Antidepressive Agents, Behavior, Animal, Brain, Cell Membrane, Depression, Electroconvulsive Therapy, Female, Humans, Male, Mice, Transgenic, Middle Aged, S100 Proteins, Neurons, Serotonin, Signal Transduction, Annexin A2, Mice, Knockout, Two-Hybrid System Techniques, Receptor, Serotonin, 5-HT1B, Mice, Rats
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