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Science 329 (5998): 1537-1541

Copyright © 2010 by the American Association for the Advancement of Science

MiR-16 Targets the Serotonin Transporter: A New Facet for Adaptive Responses to Antidepressants

Anne Baudry,1 Sophie Mouillet-Richard,1 Benoît Schneider,1 Jean-Marie Launay,2,3,* Odile Kellermann1,*

Abstract: The serotonin transporter (SERT) ensures the recapture of serotonin and is the pharmacological target of selective serotonin reuptake inhibitor (SSRI) antidepressants. We show that SERT is a target of microRNA-16 (miR-16). miR-16 is expressed at higher levels in noradrenergic than in serotonergic cells; its reduction in noradrenergic neurons causes de novo SERT expression. In mice, chronic treatment with the SSRI fluoxetine (Prozac) increases miR-16 levels in serotonergic raphe nuclei, which reduces SERT expression. Further, raphe exposed to fluoxetine release the neurotrophic factor S100β, which acts on noradrenergic cells of the locus coeruleus. By decreasing miR-16, S100β turns on the expression of serotonergic functions in noradrenergic neurons. Based on pharmacological and behavioral data, we propose that miR-16 contributes to the therapeutic action of SSRI antidepressants in monoaminergic neurons.

1 Cellules Souches, Signalisation et Prions, INSERM U747, Université Paris Descartes, 75006 Paris, France.
2 Pharma Research Department, F. Hoffmann-La-Roche, CH-4070 Basel, Switzerland.
3 Assistance Publique–Hôpitaux de Paris Service de Biochimie, RTRS Santé Mentale, U942 INSERM Hôpital Lariboisière, Paris, France.

* To whom correspondence should be addressed. E-mail: jean-marie.launay{at}lrb.aphp.fr (J.-M.L.); odile.kellermann{at}parisdescartes.fr (O.K.)

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