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.
Affiliation
1] UMR-S839 INSERM, Paris, France [2] Université Pierre et Marie Curie, Paris, France [3] Institut du Fer à Moulin, Paris, France.
Journal Details
This article was published in the following journal.
Name: Molecular psychiatry
ISSN: 1476-5578
Pages:
Links
- 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
Serotonin Antagonists
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.
PubMed Articles
Antidepressant effects of estrogens: a basic approximation.
The use of estrogenic compounds as antidepressants or as coadjuvants to facilitate the effect of antidepressants has reported controversial results, suggesting that many factors could influence their...
Pyrimidine usually has good pharmacokinetic properties as a drug substance and considerable efforts have been devoted to develop pyrimidine derivatives into drug candidates. Arylpiperazine-containing...
Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for depression. Recent reports in the literature describe differences in antidepressant effects among SSRIs. Although each SS...
The lateral septum (LS) is a limbic brain region that receives serotonergic projections from raphe neurons and participates in the modulation of stress responses and affective states. The present stud...
Our previous studies have showed that treating mice with piperine significantly decreased the immobility time of the animals in the forced swim test and tail suspension test, which was related to up-r...
Clinical Trials
Antidepressant Safety in Kids Study
This study will evaluate the risks and benefits of treatment with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor in children and adolescents with a...
Antidepressant medicines sometimes cause sexual side effects. The purpose of this study is to determine whether the sexual dysfunction sometimes caused by selective serotonin reuptake inhi...
Treatment Effects on Platelet Calcium in Hypertensive and Depressed Patients
This study aims to determine if treatment with an SSRI antidepressant medication, paroxetine, is associated with cellular calcium response to serotonin, platelet serotonin receptors, and i...
Azilect + Antidepressant Chart Review
To identify the occurrence of serotonin toxicity in Parkinson's Disease (PD) patients receiving antidepressant therapy and rasagiline, compared to those receiving rasagiline without antide...
Specific Effects of Escitalopram on Neuroendocrine Response
Citalopram, a selective serotonin reuptake inhibitor (SSRI), is used as a neuroendocrine probe in human subjects to assess serotonin (5-hydroxytryptamine; 5-HT) function as reflected in pr...
