5-HT(2B) receptors are required for serotonin-selective antidepressant actions
Description
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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| ID Code: | 75306 | ||
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| Item Type: | Contribution to Journal (Journal Article) | ||
| Refereed: | Yes | ||
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| Measurements or Duration: | 10 pages | ||
| Keywords: | 5-HT2B, SSRI, antidepressants | ||
| DOI: | 10.1038/mp.2011.159 | ||
| ISSN: | 1476-5578 | ||
| Pure ID: | 32398948 | ||
| Divisions: | Past > QUT Faculties & Divisions > Faculty of Health Past > Institutes > Institute of Health and Biomedical Innovation |
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| Copyright Owner: | Consult author(s) regarding copyright matters | ||
| Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||
| Deposited On: | 19 Aug 2014 22:43 | ||
| Last Modified: | 11 Jun 2024 20:24 |
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