Nature
April 3, 2019
Romain Nardou, Eastman M. Lewis, Rebecca Rothhaas et al.
343 citations
A critical period is a developmental window when the nervous system is especially sensitive to environmental stimuli needed for proper circuit organization and learning. In disease, closure of these periods limits the brain's ability to adapt. This work provides evidence that developmental regulation of oxytocin-mediated synaptic plasticity in the nucleus accumbens establishes a critical period for social reward learning. A single dose of MDMA reopens this critical period and upregulates oxytocin-dependent long-term depression. Reopening requires activation of oxytocin receptors in the nucleus accumbens and is recapitulated by stimulating oxytocin terminals there. These findings have implications for neurodevelopmental diseases with social impairments and disorders influenced by social factors.
Nature
June 14, 2023
Romain Nardou, Young Jun Song, Noelle Wright et al.
335 citations
Psychedelic drugs share the ability to reopen a critical period for social reward learning in adult mice, and the duration of this reopening matches the length of subjective effects in humans. The reinstatement of social reward learning is accompanied by a metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Analysis of gene expression in the open versus closed state indicates that reorganization of the extracellular matrix is a common downstream mechanism. These findings suggest a unifying mechanism for psychedelics' therapeutic properties and may guide clinical use and drug design for neuropsychiatric diseases.
bioRxiv Preprint Server
April 16, 2018
Eric Edsinger, Gül Dölen
1 citation
preprint
MDMA, also known as ecstasy, increases social behavior in octopuses, despite over 500 million years of evolutionary separation from humans. Octopuses are typically solitary, but when given MDMA, they spent more time in close contact with other octopuses. This effect is linked to a shared serotonin transporter protein, which has a binding site for MDMA that is evolutionarily conserved in the octopus genome. The findings suggest that the neural systems underlying social behavior, particularly those involving serotonin, are ancient and have been preserved across diverse animal lineages.
Annual review of neuroscience
July 1, 2026
Gül Dölen, Makenzie L Wilkinson
Psychedelics reopen critical periods, induce metaplasticity, and reorganize the extracellular matrix, which helps explain their diverse, durable, and context-dependent therapeutic effects. This neurobiological evidence challenges the biochemical imbalance model that has dominated translational neuroscience since the 1950s and supports a learning model that better accounts for psychedelics' unique therapeutic profile.