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The therapeutic effects induced by serotonin-selective reuptake inhibitor (SSRI) antidepressants are initially triggered by blocking the serotonin transporter and rely on long-term adaptations of pre- and post-synaptic receptors. We show here that long-term behavioral and neurogenic SSRI effects are abolished after either genetic or pharmacological inactivation of 5-HT(2B) receptors. Conversely, direct agonist stimulation of 5-HT(2B) receptors induces an SSRI-like response in behavioral and neurogenic assays. Moreover, the observation that (i) this receptor is expressed by raphe serotonergic neurons, (ii) the SSRI-induced increase in hippocampal extracellular serotonin concentration is strongly reduced in the absence of functional 5-HT(2B) receptors and (iii) a selective 5-HT(2B) agonist mimics SSRI responses, supports a positive regulation of serotonergic neurons by 5-HT(2B) receptors. The 5-HT(2B) receptor appears, therefore, to positively modulate serotonergic activity and to be required for the therapeutic actions of SSRIs. Consequently, the 5-HT(2B) receptor should be considered as a new tractable target in the combat against depression.
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
September 2011,
Neuropharmacology,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
May 2001,
Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
October 1988,
The Journal of pharmacology and experimental therapeutics,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
March 2008,
The Journal of neuroscience : the official journal of the Society for Neuroscience,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
July 2003,
Journal of medicinal chemistry,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
March 2004,
European journal of pharmacology,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
August 1999,
IDrugs : the investigational drugs journal,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
March 2001,
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
January 2000,
Molecular pharmacology,
S L Diaz, and
S Doly, and
N Narboux-Nême, and
S Fernández, and
P Mazot, and
S M Banas, and
K Boutourlinsky, and
I Moutkine, and
A Belmer, and
A Roumier, and
L Maroteaux
November 2000,
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience,
