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Science 301 (5634): 805-809

Copyright © 2003 by the American Association for the Advancement of Science

Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants

Luca Santarelli,1* Michael Saxe,1* Cornelius Gross,1 Alexandre Surget,2 Fortunato Battaglia,3 Stephanie Dulawa,1 Noelia Weisstaub,1 James Lee,1 Ronald Duman,4 Ottavio Arancio,3 Catherine Belzung,2 René Hen1{dagger}

Abstract: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.

1 Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
2 Psychobiologie des Emotions, Université François Rabelais, Tours 37200, France.
3 Nathan Kline Research Institute, New York University School of Medicine, New York, NY 10016, USA.
4 Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University, New Haven, CT 06508, USA.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: rh95{at}columbia.edu


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M. K. Gupta, R. S. Papay, C. W. D. Jurgens, R. J. Gaivin, T. Shi, V. A. Doze, and D. M. Perez (2009)
Mol. Pharmacol. 76, 314-326
   Abstract »    Full Text »    PDF »
A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation.
C. D. Clelland, M. Choi, C. Romberg, G. D. Clemenson Jr., A. Fragniere, P. Tyers, S. Jessberger, L. M. Saksida, R. A. Barker, F. H. Gage, et al. (2009)
Science 325, 210-213
   Abstract »    Full Text »    PDF »
Induction of Neuronal Vascular Endothelial Growth Factor Expression by cAMP in the Dentate Gyrus of the Hippocampus Is Required for Antidepressant-Like Behaviors.
J.-S. Lee, D.-J. Jang, N. Lee, H.-G. Ko, H. Kim, Y.-S. Kim, B. Kim, J. Son, S. H. Kim, H. Chung, et al. (2009)
J. Neurosci. 29, 8493-8505
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A proteomic investigation of similarities between conventional and herbal antidepressant treatments.
K Pennington, M Focking, C. McManus, C. Pariante, M. Dunn, and D. Cotter (2009)
J Psychopharmacol 23, 520-530
   Abstract »    PDF »
GABA-cAMP Response Element-Binding Protein Signaling Regulates Maturation and Survival of Newly Generated Neurons in the Adult Hippocampus.
R. Jagasia, K. Steib, E. Englberger, S. Herold, T. Faus-Kessler, M. Saxe, F. H. Gage, H. Song, and D. C. Lie (2009)
J. Neurosci. 29, 7966-7977
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A New Role for FGF2 as an Endogenous Inhibitor of Anxiety.
J. A. Perez, S. M. Clinton, C. A. Turner, S. J. Watson, and H. Akil (2009)
J. Neurosci. 29, 6379-6387
   Abstract »    Full Text »    PDF »
Reviews: Mechanisms Mediating Brain Plasticity: IGF1 and Adult Hippocampal Neurogenesis.
M. LLorens-Martin, I. Torres-Aleman, and J. L. Trejo (2009)
Neuroscientist 15, 134-148
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Identification of Small-Molecule Modulators of Mouse SVZ Progenitor Cell Proliferation and Differentiation Through High-Throughput Screening.
Y. Liu, R. Lacson, J. Cassaday, D. A. Ross, A. Kreamer, E. Hudak, R. Peltier, D. Mclaren, I. Munoz-Sanjuan, F. Santini, et al. (2009)
J Biomol Screen 14, 319-329
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Effects of bifeprunox and aripiprazole on rat serotonin and dopamine neuronal activity and anxiolytic behaviour.
L Dahan, H Husum, O Mnie-Filali, J Arnt, P Hertel, and N Haddjeri (2009)
J Psychopharmacol 23, 177-189
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Mechanisms of Neurodegeneration and Regeneration in Alcoholism.
F. T. Crews and K. Nixon (2009)
Alcohol Alcohol. 44, 115-127
   Abstract »    Full Text »    PDF »
Prolactin Prevents Chronic Stress-Induced Decrease of Adult Hippocampal Neurogenesis and Promotes Neuronal Fate.
L. Torner, S. Karg, A. Blume, M. Kandasamy, H.-G. Kuhn, J. Winkler, L. Aigner, and I. D. Neumann (2009)
J. Neurosci. 29, 1826-1833
   Abstract »    Full Text »    PDF »
Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats.
S. Jessberger, R. E. Clark, N. J. Broadbent, G. D. Clemenson Jr, A. Consiglio, D. C. Lie, L. R. Squire, and F. H. Gage (2009)
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   Abstract »    Full Text »    PDF »

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