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5-HT(2B) receptors are required for serotonin-selective antidepressant actions.

Abstract : 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.
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Submitted on : Thursday, June 14, 2012 - 8:33:45 AM
Last modification on : Wednesday, February 24, 2021 - 12:32:02 PM
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Silviana Laura Diaz, Stéphane Doly, Nicolas Narboux-Nême, Sébasatien Fernández, Pierre Mazot, et al.. 5-HT(2B) receptors are required for serotonin-selective antidepressant actions.. Molecular Psychiatry, Nature Publishing Group, 2012, 17 (2), pp.154-63. ⟨10.1038/mp.2011.159⟩. ⟨inserm-00652573⟩



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