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Published on: December 22, 2008
MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens
Ben Rein1, Kendall Raymond1, Cali Boustani2
1Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
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.
Insights
MDMA, or 3,4-methylenedioxymethamphetamine, enhances empathy-like behaviors in mice by acting on serotonin signaling in the nucleus accumbens. This research sheds light on MDMA's potential as an empathogen.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- 3,4-methylenedioxymethamphetamine (MDMA) is known for prosocial effects, but its empathogenic properties and mechanisms remain unclear.
- Empathy is crucial for social behavior, and deficits are observed in conditions like autism.
Purpose of the Study:
- To investigate the empathogenic effects of MDMA in mice.
- To elucidate the neurobiological mechanisms underlying MDMA's prosocial actions, particularly serotonin (5-HT) signaling in the nucleus accumbens (NAc).
- To assess MDMA's potential to restore empathy deficits in a mouse model of autism.
Main Methods:
- Utilized social transfer of pain and analgesia tests to model empathy in mice.
- Employed region-specific neuropharmacology, optogenetics, and transgenic manipulations.
- Investigated the role of 5-HT signaling in the NAc.
Main Results:
- MDMA administration (systemic or NAc-infused) significantly enhanced social transfer of pain and analgesia.
- Optogenetic stimulation of 5-HT release in the NAc mimicked MDMA's empathogenic effects.
- MDMA and NAc 5-HT stimulation ameliorated empathy deficits in Shank3-deficient mice.
Conclusions:
- MDMA robustly enhances empathy-related behaviors in mice.
- Serotonin signaling within the nucleus accumbens is a key mechanism mediating MDMA's empathogenic effects.
- MDMA shows potential for restoring empathy deficits, particularly in models of autism spectrum disorder.
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