Psychedelics reopen the social reward learning critical period
Summary & key facts
Researchers gave different psychedelic drugs to mice and found the drugs could reopen a window of brain plasticity used for learning social rewards. This reopened window went along with changes in a social hormone system in a key reward area of the brain and with changes in genes that control the brain’s scaffolding. The timing of the reopened window matched how long people report feeling the drugs, which suggests a shared biological effect across psychedelics. The work is in mice, so it points to possible ideas for therapy but does not prove the same effects happen in people.
- The team tested several psychedelic drugs in mice and found all of them could reopen a so-called critical period for social reward learning. A critical period is a time when the brain is extra good at learning certain things, and this windo
- The length of time that the critical period stayed open in mice matched the usual duration of acute subjective effects that people report after taking the same drugs. That is a correlation across species, not proof the same happens in human
- Reopening social learning was linked to restoring a form of brain plasticity that depends on oxytocin, a hormone tied to social behavior. This plasticity occurred in the nucleus accumbens, a brain area involved in reward.
- When the brain was in the reopened state, the researchers found different patterns of gene activity that point to reorganization of the extracellular matrix. The extracellular matrix is the network of molecules around brain cells that helps
- Because these effects appeared across different psychedelic drugs, the authors suggest a common downstream mechanism that could matter for designing therapies or new compounds. However, the experiments were done in mice, so we cannot assume
Abstract
Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness1,2. 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 therapies3-9. 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.