MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens.
Ben Rein, Kendall Raymond, Cali Boustani, Sabrena Tuy, Jie Zhang, Robyn St Laurent, Matthew B Pomrenze, Parnaz Boroon, Boris D. Heifets, Monique L. Smith, Robert C. Malenka
Science Advances April 26, 2024 DOI: 10.1126/sciadv.adl6554 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | MDMA |
| Topics | MDMA Serotonin |
| Keywords | Psychopharmacology MDMA Research Behavioral science Empathy studies |
| Citations | 37 |
| Key findings | MDMA enhances empathy-related behaviors in mice through serotonin signaling in the nucleus accumbens. |
Abstract
MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 19
- The efficacy and safety of MDMA-assisted psychotherapy for treatment of posttraumatic stress disorder: A systematic review and meta-analysis from randomized controlled trials. Psychiatry Research September 1, 2024
- Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications Pharmaceuticals January 19, 2025
- From Efficacy to Effectiveness: Evaluating Psychedelic Randomized Controlled Trials for Trustworthy Evidence‐Based Policy and Practice Pharmacology Research & Perspectives April 1, 2025
- Stereoselective, sex-dependent 5-HT2A receptor modulation of cortical plasticity by MDMA in mice. Neuropsychopharmacology February 2, 2026
- History, pharmacology and therapeutic mechanisms of 3,4‐methylenedioxymethamphetamine (MDMA) British Journal of Pharmacology October 21, 2025
and 14 more in the library
Cites 16
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- Gender differences in the subjective effects of MDMA Psychopharmacology March 5, 2001
- MDMA enhances emotional empathy and prosocial behavior Social Cognitive and Affective Neuroscience October 4, 2013
and 11 more in the library