| Literature DB >> 22158014 |
S L Diaz1, S Doly, N Narboux-Nême, S Fernández, P Mazot, S M Banas, K Boutourlinsky, I Moutkine, A Belmer, A Roumier, L Maroteaux.
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.Entities:
Mesh：
Substances：
Year: 2011 PMID： 22158014 PMCID： PMC3381222 DOI： 10.1038/mp.2011.159
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 15.992