Serotonin 5-HT2BReceptors Are Required for 3,4-Methylenedioxymethamphetamine-Induced Hyperlocomotion and 5-HT ReleaseIn VivoandIn Vitro
Stéphane Doly, Emmanuel Valjent, Vincent Setola, Jacques Callebert, Denis Hervé, Jean‐marie Launay, Luc Maroteaux
Journal of Neuroscience March 12, 2008 DOI: 10.1523/jneurosci.5723-07.2008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Topics | MDMA Serotonin |
| Keywords | 5-HT Receptor Pharmacology Postsynaptic potential Serotonin transporter Endogenous agonist |
| Citations | 140 |
| Key findings | Blocking or removing the 5-HT2B receptor in mice completely abolishes MDMA-induced hyperlocomotion and serotonin release in brain regions involved in reward. |
Abstract
The “club drug” 3,4-methylenedioxymethamphetamine (MDMA; also known as ecstasy) binds preferentially to and reverses the activity of the serotonin transporter, causing release of serotonin [5-hydroxytryptamine (5-HT)] stores from nerve terminals. Subsequent activation of postsynaptic 5-HT receptors by released 5-HT has been shown to be critical for the unique psychostimulatory effects of MDMA. In contrast, the effects of direct activation of presynaptic and/or postsynaptic receptors by MDMA have received far less attention, despite the agonist actions of the drug itself at 5-HT 2 receptors, in particular the 5-HT 2B receptor. Here we show that acute pharmacological inhibition or genetic ablation of the 5-HT 2B receptor in mice completely abolishes MDMA-induced hyperlocomotion and 5-HT release in nucleus accumbens and ventral tegmental area. Furthermore, the 5-HT 2B receptor dependence of MDMA-stimulated release of endogenous 5-HT from superfused midbrain synaptosomes suggests that 5-HT 2B receptors act, unlike any other 5-HT receptor, presynaptically to affect MDMA-stimulated 5-HT release. Thus, our findings reveal a novel regulatory component in the actions of MDMA and represent the first demonstration that 5-HT 2B receptors play an important role in the brain, i.e., modulation of 5-HT release. As such, 5-HT 2B receptor antagonists may serve as promising therapeutic drugs for MDMA abuse.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 30
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA Cell Discovery October 5, 2018
- Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice PLoS One November 20, 2009
- Therapeutic mechanisms of psychedelics and entactogens. Neuropsychopharmacology July 24, 2023
- MDMA and MDMA-Assisted Therapy. American Journal of Psychiatry 2025
and 25 more in the library
Cites 5
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- Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions Journal of Neurochemistry 1996
- Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release Journal of Neurochemistry October 27, 2004
- 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro. Molecular Pharmacology June 2003
- The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens. Pharmacology, Biochemistry, and Behavior April 1998