Related Experiment Video
Updated: May 26, 2026

Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
5-HT(2B) receptors are required for serotonin-selective antidepressant actions
S L Diaz1, S Doly, N Narboux-Nême
1UMR-S839 INSERM, Paris, France.
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.
Related Concept Videos
Antidepressant Drugs: MAOIs and Other Agents
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
G-protein Coupled Receptors
Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
Antidepressant Drugs: Overview
Drugs Affecting Neurotransmitter Release or Uptake