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

Diaz, S. L., Doly, S., Narboux-Nême, N., Fernandez, S., Mazot, P., Banas, S. M., Boutourlinsky, K., Moutkine, I., Belmer, A., Roumier, A., & Maroteaux, L. (2012) 5-HT(2B) receptors are required for serotonin-selective antidepressant actions. Molecular Psychiatry, 17(2), pp. 154-163.

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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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64 citations in Web of Science®

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ID Code: 75306
Item Type: Journal Article
Refereed: Yes
Keywords: 5-HT2B, antidepressants, SSRI
DOI: 10.1038/mp.2011.159
ISSN: 1476-5578
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > NEUROSCIENCES (110900) > Neurosciences not elsewhere classified (110999)
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 19 Aug 2014 22:43
Last Modified: 21 Aug 2014 00:59

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