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Science 8 August 2003:
Vol. 301. no. 5634, pp. 805 - 809
DOI: 10.1126/science.1083328
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Research Articles

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}

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.


* These authors contributed equally to this work.

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

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Science. ISSN 0036-8075 (print), 1095-9203 (online)