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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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Enhanced Adult Neurogenesis and Angiogenesis and Altered Affective Behaviors in Mice Overexpressing Vascular Endothelial Growth Factor 120.
H. Udo, Y. Yoshida, T. Kino, K. Ohnuki, W. Mizunoya, T. Mukuda, and H. Sugiyama (2008)
J. Neurosci. 28, 14522-14536
   Abstract »    Full Text »    PDF »
Adult Neurogenesis, Mental Health, and Mental Illness: Hope or Hype?.
A. J. Eisch, H. A. Cameron, J. M. Encinas, L. A. Meltzer, G.-L. Ming, and L. S. Overstreet-Wadiche (2008)
J. Neurosci. 28, 11785-11791
   Abstract »    Full Text »    PDF »
Physical Interaction of Calmodulin with the 5-Hydroxytryptamine2C Receptor C-Terminus Is Essential for G Protein-independent, Arrestin-dependent Receptor Signaling.
M. Labasque, E. Reiter, C. Becamel, J. Bockaert, and P. Marin (2008)
Mol. Biol. Cell 19, 4640-4650
   Abstract »    Full Text »    PDF »
Noggin Expands Neural Stem Cells in the Adult Hippocampus.
M. A. Bonaguidi, C.-Y. Peng, T. McGuire, G. Falciglia, K. T. Gobeske, C. Czeisler, and J. A. Kessler (2008)
J. Neurosci. 28, 9194-9204
   Abstract »    Full Text »    PDF »
Antipsychotic Drugs: Comparison in Animal Models of Efficacy, Neurotransmitter Regulation, and Neuroprotection.
J. A. Lieberman, F. P. Bymaster, H. Y. Meltzer, A. Y. Deutch, G. E. Duncan, C. E. Marx, J. R. Aprille, D. S. Dwyer, X.-M. Li, S. P. Mahadik, et al. (2008)
Pharmacol. Rev. 60, 358-403
   Abstract »    Full Text »    PDF »
Enhanced contextual fear memory in central serotonin-deficient mice.
J.-X. Dai, H.-L. Han, M. Tian, J. Cao, J.-B. Xiu, N.-N. Song, Y. Huang, T.-L. Xu, Y.-Q. Ding, and L. Xu (2008)
PNAS 105, 11981-11986
   Abstract »    Full Text »    PDF »
Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus.
E. Segi-Nishida, J. L. Warner-Schmidt, and R. S. Duman (2008)
PNAS 105, 11352-11357
   Abstract »    Full Text »    PDF »
Cognitive Role of Neurogenesis in Depression and Antidepressant Treatment.
T. D. Perera, S. Park, and Y. Nemirovskaya (2008)
Neuroscientist 14, 326-338
   Abstract »    PDF »
Exercise-induced promotion of hippocampal cell proliferation requires {beta}-endorphin.
M. Koehl, P. Meerlo, D. Gonzales, A. Rontal, F. W. Turek, and D. N. Abrous (2008)
FASEB J 22, 2253-2262
   Abstract »    Full Text »    PDF »
Leptin Increases Adult Hippocampal Neurogenesis in Vivo and in Vitro.
J. C. Garza, M. Guo, W. Zhang, and X.-Y. Lu (2008)
J. Biol. Chem. 283, 18238-18247
   Abstract »    Full Text »    PDF »
Chronic Fluoxetine Bidirectionally Modulates Potentiating Effects of Serotonin on the Hippocampal Mossy Fiber Synaptic Transmission.
K. Kobayashi, Y. Ikeda, E. Haneda, and H. Suzuki (2008)
J. Neurosci. 28, 6272-6280
   Abstract »    Full Text »    PDF »
Latent Stem and Progenitor Cells in the Hippocampus Are Activated by Neural Excitation.
T. L. Walker, A. White, D. M. Black, R. H. Wallace, P. Sah, and P. F. Bartlett (2008)
J. Neurosci. 28, 5240-5247
   Abstract »    Full Text »    PDF »

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