3,4-N-methlenedioxymethamphetamine-induced hypophagia is maintained in 5-HT1B receptor knockout mice, but suppressed by the 5-HT2C receptor antagonist RS102221.
Grégory Conductier, Cyril Crosson, René Hen, Joël Bockaert, Valérie Compan
Neuropsychopharmacology June 2005 DOI: 10.1038/sj.npp.1300662 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Mice (including 5-HT1B receptor-null mice and wild-type) |
| Interventions | MDMA GR127935 RS102221 |
| Dose | MDMA 10 mg/kg; GR127935 3 or 10 mg/kg; RS102221 2 mg/kg |
| Topics | Serotonin |
| Key findings | MDMA (10 mg/kg) in starved mice caused an initial hypophagia (-77% for 1 h) followed by hyperphagia (1-3 h). The 5-HT2C antagonist RS102221 (2 mg/kg) blocked the hypophagia and MDMA-induced hyperlocomotion, but not the hyperphagia; 5-HT1B deletion or antagonism did not alter feeding responses. |
Abstract
3,4-Methylenedioxy-N-methamphetamine (MDMA or 'ecstasy') is a psychoactive substance, first described as an appetite suppressant in humans, inducing side effects and even death. MDMA increases serotonin (5-HT) levels, and 5-HT inhibits food intake, but the 5-HT receptors involved in MDMA-induced changes in feeding behavior are unknown. We examined whether a systemic MDMA injection would reduce the physiological drive to eat in starved mice and tested if the inactivation of 5-HT1B or 5-HT2C receptors could restore this response. Our results indicate that in starved mice, MDMA (10 mg/kg) provoked an initial hypophagia for 1 h (-77%) followed by a period of hyperphagia (studied between 1 and 3 h). This biphasic feeding behavior due to MDMA treatment was maintained in 5-HT1B receptor-null mice or in animals treated with the 5-HT1B/1D receptor antagonist GR127935 (3 or 10 mg/kg). In contrast, MDMA-induced hypophagia (for the first 1 h period) was suppressed when combined with the 5-HT2C receptor antagonist RS102221 (2 mg/kg). However, RS102221 did not alter MDMA-induced hyperphagia (for the 1-3 h period) but did exert a stimulant effect, when administered alone, during that period. We have previously shown that MDMA or 5-HT1A/1B receptor agonist RU24969 fails to stimulate locomotor activity in 5-HT1B receptor-null mice. Our present data indicate that the 5-HT2C receptor antagonist RS102221 suppresses MDMA-induced hyperlocomotion. These findings provide the first evidence that the inactivation of 5-HT2C receptors may reduce hypophagia and motor response to MDMA, while a genetic deficit or pharmacological inactivation of 5-HT1B receptors was insufficient to alter the feeding response to MDMA.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
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- The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice. Molecular Psychiatry May 1, 2026
- A repeated low-dose regimen of MDMA has transient next-day effects on locomotor activity, anxiety-like behavior, and brain serotonin levels, with no effect on anhedonia-like behavior, in both female and male rats Psychopharmacology March 4, 2026
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- A genetic reduction in the serotonin transporter differentially influences MDMA and heroin induced behaviours. Psychopharmacology July 2018
- Reduced Efficacy of d-Amphetamine and 3,4-Methylenedioxymethamphetamine in Inducing Hyperactivity in Mice Lacking the Postsynaptic Scaffolding Protein SHANK1. Frontiers in Molecular Neuroscience 2018
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Cites 7
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- Potential Human Neurotoxicity of MDMA (‘Ecstasy’): Subjective Self-Reports, Evidence from an Italian Drug Addiction Centre and Clinical Case Studies Neuropsychobiology 2000
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