Psychedelics reopen the social reward learning critical period
Romain Nardou, Young Jun Song, Noelle Wright, Carine Lama, Sehr Faltin, Gül Dölen, Edward J. Sawyer, M. F. Wilkinson, Yasmin Padovan‐hernandez, Júnia L. de Deus, Loyal A. Goff, Genevieve Stein-O’Brien
Nature June 14, 2023 DOI: 10.1038/s41586-023-06204-3 via OpenAlex
Summary
AI-generated from the abstractPsychedelic 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.
Study at a glance
| Characteristics | Experimental study in mice Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Psychedelic drugs |
| Topics | Addiction Psilocybin |
| Keywords | Mechanism biology Period music Nucleus accumbens Psychology |
| Citations | 335 |
| Key finding | Psychedelic drugs reopen the social reward learning critical period in mice, with a time course proportional to human subjective effects, mediated by oxytocin-dependent plasticity and extracellular matrix reorganization. |
Abstract
Abstract Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness 1,2 . These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies 3–9 . Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the ‘open state’ versus the ‘closed state’ provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.