5-HT(2B) receptors are required for serotonin-selective antidepressant actions.
Summary of "5-HT(2B) receptors are required for serotonin-selective antidepressant actions."
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.Molecular Psychiatry advance online publication, 13 December 2011; doi:10.1038/mp.2011.159.
1] UMR-S839 INSERM, Paris, France  Université Pierre et Marie Curie, Paris, France  Institut du Fer à Moulin, Paris, France.
This article was published in the following journal.
Name: Molecular psychiatry
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22158014
- DOI: http://dx.doi.org/10.1038/mp.2011.159
Medical and Biotech [MESH] Definitions
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonin agonists.
Serotonin 5-ht3 Receptor Antagonists
Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.
Serotonin 5-ht4 Receptor Antagonists
Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.
Receptors, Serotonin, 5-ht3
A subclass of serotonin receptors that form cation channels and mediate signal transduction by depolarizing the cell membrane. The cation channels are formed from 5 receptor subunits. When stimulated the receptors and allow the selective passage of SODIUM; POTASSIUM; and CALCIUM.
Serotonin 5-ht2 Receptor Antagonists
Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.
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