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 |
| 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.