Psychedelics unlock learning windows in the brain

Summary: Researchers have discovered a unique property of psychedelic drugs: their ability to reopen “critical periods” in the brain, times when the brain is highly sensitive to environmental learning cues. These periods, usually associated with the development of skills like language learning, are reopened by psychedelics for different durations.

This breakthrough in understanding the function of psychedelic drugs may have therapeutic implications for conditions such as stroke and deafness. In addition, he discovers new molecular mechanisms influenced by psychedelics.

Highlights:

1. Psychedelic drugs, including ibogaine, ketamine, LSD, MDMA and psilocybin, can reopen “critical periods” of brain development in mice, making them more receptive to learning from their environment.
2. The duration of these reopened critical periods varies depending on the psychedelic drug used, ranging from 48 hours with ketamine to four weeks with ibogaine.
3. The study also identified molecular mechanisms influenced by psychedelics, including 65 protein-producing genes that show differences in expression during and after the critical period.

Source: Johns Hopkins University

Neuroscientists have long searched for ways to reopen “critical periods” in the brain, when mammals are more sensitive to signals from their environment that can influence periods of brain development.

Now, Johns Hopkins Medicine researchers say a new mouse study shows that psychedelic drugs are linked by their common ability to reopen such critical periods, but differ in how long the critical period is open – by two days to four weeks with a single dose.

The results, published on June 14 in the journal Natureprovide a new explanation for how psychedelic drugs work, scientists say, and suggest potential for treating a wider range of conditions, such as stroke and deafness, beyond those of current drug studies, such as as depression, substance abuse and post-traumatic effects. stress disorder.

Scientists also offer a new look at the molecular mechanisms impacted by psychedelics.

Critical periods have been shown to perform functions such as helping birds learn to sing and helping humans learn a new language, relearning motor skills after a stroke, and establishing the dominance of one eye over the eye. other eye.

“There is a window of time where the mammalian brain is much more susceptible and open to learning from the environment,” says Gül Dölen, MD, Ph.D., associate professor of neuroscience at Johns Hopkins University School. of Medicine.

“That window will close at some point, and then the brain will become much less open to new learning.”

Drawing on his lab’s experience in studying social behavior, Dölen’s team investigated how psychedelic drugs work by reopening these critical periods. In 2019, his team discovered that MDMA, a psychedelic drug that elicits feelings of love and sociability, opens a critical period in mice.

At the time, Dölen thought that the prosocial properties of MDMA facilitated the opening of the critical period, but her team was surprised, she says, to find in the current study that other psychedelic drugs without prosocial properties could also reopen critical periods.

For the current study, Dölen’s team examined the reopening potential of five psychedelic drugs – ibogaine, ketamine, LSD, MDMA and psylocibin – shown in numerous studies to be able to change normal perceptions. of existence and to allow a sense of discovery about oneself or the world.

The research team conducted a well-established behavioral test to understand how easily adult male mice learn from their social environment. They trained mice to develop an association between an environment related to social interaction and another environment related to autonomy.

By comparing the time spent in each environment after giving the psychedelic drug to the mice, the researchers were able to see if the critical period opened up in the adult mice, allowing them to learn the value of a social environment – a behavior normally learned as juveniles.

For mice given ketamine, the critical social reward learning period remained open in the mice for 48 hours. With psilocybin, the open state lasted two weeks. For mice given MDMA, LSD, and ibogaine, the critical period remained open for two, three, and four weeks, respectively.

The researchers say that the length of time the critical period remained open in the mice appears to roughly parallel the average length of time people self-report the acute effects of each psychedelic drug.

“This relationship gives us another clue that the duration of the acute effects of psychedelic drugs may be why each drug may have longer or shorter effects on the onset of the critical period,” says Dölen.

“The open state of the critical period can be an opportunity for a post-treatment integration period to maintain the learning state,” she adds.

“Too often, after undergoing a procedure or treatment, people return to their chaotic and busy lives which can be overwhelming. Clinicians may want to consider the period after a dose of psychedelic drugs as a period of healing and learning, much like we do with open-heart surgery.

Next, scientists studied the impact of psychedelic drugs on molecular mechanisms. First, in mouse brain cells, they looked at a binding point, called a receptor, for the neurotransmitter serotonin.

Researchers have found that while LSD and psilocybin use the serotonin receptor to open the critical period, MDMA, ibogaine and ketamine do not.

To explore other molecular mechanisms, the research team turned to ribonucleic acid (RNA), a cousin of DNA that represents the genes that are expressed (producing proteins) in mouse cells.

The researchers found expression differences among 65 protein-producing genes during and after the onset of the critical period.

About 20% of these genes regulate proteins involved in maintaining or repairing the extracellular matrix, a kind of scaffolding that envelops brain cells located in the nucleus accumbens, an area associated with social learning behaviors that respond to rewards. .

Others who helped conduct the research were Romain Nardou, Edward Sawyer, Young Jun Song, Makenzie Wilkinson, Yasmin Padovan-Hernandez, Júnia Lara de Deus, Noelle Wright, Carine Lama, Sehr Faltin, Loyal Goff and Genevieve Stein-O ‘Brien from Johns Hopkins.

About this psychopharmacology and neuroscience research news

Author: Rose fertilizer
Source: Johns Hopkins Medicine
Contact: Rose Dolen – Johns Hopkins Medicine
Picture: Image is credited to Neuroscience News

Original research: Access closed.
“Psychedelics reopen the critical learning period of social reward” by Gul Dolen et al. Nature

Abstract

Psychedelics reopen the critical learning period of social reward

Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness.

These drugs have been used for millennia in spiritual and medicinal contexts, and a number of recent clinical successes have sparked renewed interest in the development of psychedelic therapies.

Nevertheless, a unifying mechanism that could account for these shared phenomenological and therapeutic properties remains unknown.

Here, we demonstrate in mice that the ability to reopen the critical social reward learning period is a shared property among psychedelic drugs. In particular, the time course of the reopening of the critical period is proportional to the duration of the acute subjective effects reported in humans.

Furthermore, the ability to restore social reward learning in adulthood is accompanied by metaplastic restoration of long-term oxytocin-mediated depression in the nucleus accumbens.

Finally, the identification of differentially expressed genes in the “open state” versus the “closed state” provides evidence that extracellular matrix reorganization is a common downstream mechanism underlying period reopening. criticism mediated by psychedelic drugs.

Together, these results have important implications for the implementation of psychedelics in clinical practice, as well as for the design of new compounds for the treatment of neuropsychiatric diseases.