Oxytocin-dependent reopening of a social reward learning critical period with MDMA
Romain Nardou, Eastman M. Lewis, Rebecca Rothhaas, Ran Xu, Aimei Yang, Edward Boyden, Gül Dölen
Nature April 3, 2019 DOI: 10.1038/s41586-019-1075-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Intervention | MDMA |
| Dose | a single dose |
| Topics | MDMA |
| Citations | 343 |
| Post-publication review | 3 comments on PubPeer (opens in new tab) · last active June 2019 |
| Key findings | Developmental regulation of oxytocin-mediated synaptic plasticity in the nucleus accumbens establishes a critical period for social reward learning, and a single dose of MDMA reopens this critical period via oxytocin receptor activation. |
Abstract
A critical period is a developmental epoch during which the nervous system is expressly sensitive to specific environmental stimuli that are required for proper circuit organization and learning. Mechanistic characterization of critical periods has revealed an important role for exuberant brain plasticity during early development, and for constraints that are imposed on these mechanisms as the brain matures1. In disease states, closure of critical periods limits the ability of the brain to adapt even when optimal conditions are restored. Thus, identification of manipulations that reopen critical periods has been a priority for translational neuroscience2. Here we provide evidence that developmental regulation of oxytocin-mediated synaptic plasticity (long-term depression) in the nucleus accumbens establishes a critical period for social reward learning. Furthermore, we show that a single dose of (+/-)-3,4-methylendioxymethamphetamine (MDMA) reopens the critical period for social reward learning and leads to a metaplastic upregulation of oxytocin-dependent long-term depression. MDMA-induced reopening of this critical period requires activation of oxytocin receptors in the nucleus accumbens, and is recapitulated by stimulation of oxytocin terminals in the nucleus accumbens. These findings have important implications for understanding the pathogenesis of neurodevelopmental diseases that are characterized by social impairments and of disorders that respond to social influence or are the result of social injury3.
Comparable studies
Other experimental studies on MDMA, most cited first.
Citations in the library
Cited by 145
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific Reports February 10, 2020
- Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry November 8, 2021
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
- Reviewing the Potential of Psychedelics for the Treatment of PTSD The International Journal of Neuropsychopharmacology March 12, 2020
and 140 more in the library
Cites 7
- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
- 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. The Lancet Psychiatry May 1, 2018
- Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA) Psychopharmacology July 24, 2017
- Potential Psychiatric Uses for MDMA Clinical Pharmacology & Therapeutics November 10, 2016
- The effect of 3,4‐methylenedioxymethamphetamine (MDMA, ?ecstasy?) and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus British Journal of Pharmacology February 1, 2002
and 2 more in the library