Psychedelics Unlock Learning Windows in the Brain

summary: Researchers have discovered unique properties of psychedelic drugs. It is the ability to reactivate the “critical period” in the brain, a time when the brain is highly sensitive to environmental learning signals. These periods are usually associated with the development of skills such as language learning, but are resumed by psychedelics over varying periods of time.

This breakthrough in understanding the function of psychedelic drugs could help treat conditions such as stroke and hearing loss. In addition, new molecular mechanisms affected by psychedelics are also revealed.

Important facts:

1. Hallucinogens such as ibogaine, ketamine, LSD, MDMA and psilocybin may restart the ‘critical period’ of brain development in mice, making them more receptive to learning from the environment.
2. The length of these critical re-opening periods depends on the hallucinogen used: 48 hours for ketamine and 4 weeks for ibogaine.
3. The study also identified the molecular mechanisms affected by psychedelics, including 65 protein-producing genes that show differential expression during and after the critical period.

sauce: Johns Hopkins University

Neuroscientists have long sought ways to restart the brain’s “critical period.” This critical period is when mammals become sensitive to signals from their surroundings that can affect brain development.

Now, in a new study in mice, researchers at Johns Hopkins School of Medicine show that psychedelic drugs are related by a common ability to reopen such critical periods, but differ in how long the critical periods open. In other words, it was shown that the period during which the critical period opens is from 2 days to 4 weeks. Single dose.

Findings were published in the journal on June 16 NatureScientists offer new explanations for how psychedelic drugs work, and beyond the diseases currently researched on psychedelic drugs, such as depression, addiction and post-traumatic symptoms, to stroke and stroke. It suggests the potential to treat a wider range of conditions, such as hearing loss, he said. stress disorder.

Scientists are also providing new insights into the molecular mechanisms affected by psychedelic substances.

Critical periods help birds learn songs, help humans learn new languages, relearn motor skills after a stroke, and perform functions such as giving one eye dominance over the other. proven to fulfill.

“There are periods when the mammalian brain is much more sensitive and open to learning from the environment,” says Gul Dohlen, M.D., Ph.D., associate professor of neuroscience at Johns Hopkins University School of Medicine.

“This window closes at some point, after which the brain becomes less open to new learning.”

Dalen’s team has studied how psychedelic drugs work by reopening these critical periods, building on the experience of the lab that studied social behavior. In 2019, her team found that MDMA, a hallucinogen that evokes affection and sociability, causes critical periods in mice.

At the time, Doren thought that MDMA’s prosocial properties would smooth the way to restarting the critical period, but her team in the current study also found that other psychedelic drugs without prosocial properties could also be critical. She said she was surprised to discover that her period could be restarted.

In this study, Doren’s team looked at five hallucinogenic drugs (ibogaine, ketamine, LSD, MDMA, and psilocybin) were considered. 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 associations between an environment associated with social interaction and another associated with being alone.

By comparing the time spent in each environment after mice were given a hallucinogenic drug, the researchers found that a critical period opens up in adult mice, allowing them to learn the value of their social environment, which is usually when they were juveniles. I was able to confirm whether I could learn the behavior to do.

In ketamine-treated mice, the critical period for social reward learning remained open in mice for 48 h. For psilocybin, the open state lasted him two weeks. The critical period remained open for 2, 3, and 4 weeks in mice treated with MDMA, LSD, and ibogaine, respectively.

The researchers say the length of time the critical period was open in mice appears to be roughly comparable to 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 the reason why each drug has a longer or shorter effect in initiating the critical period,” says Dalen. says Mr.

“The open critical period could be an opportunity for the post-treatment consolidation period to maintain the learning state,” she added.

“Often, after undergoing a procedure or therapy, people return to a chaotic, busy life and feel overwhelmed. Think of it as a learning time.”

Scientists then investigated the effects of psychedelic drugs on molecular mechanisms. First, they looked at junctions known as receptors for the neurotransmitter serotonin in mouse brain cells.

The researchers found that LSD and psilocybin use serotonin receptors to open the critical period, but MDMA, ibogaine, and ketamine do not use serotonin receptors.

To explore other molecular mechanisms, the researchers turned to ribonucleic acid (RNA), a cousin of DNA that tells which genes are expressed (making proteins) in mouse cells.

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

Approximately 20% of these genes control proteins involved in extracellular matrix maintenance or repair. The extracellular matrix is ​​a type of scaffold that envelops brain cells in the nucleus accumbens, a region associated with reward-responsive social learning behavior.

Other members who helped conduct the research were Romain Nardu, Edward Sawyer, Young Jun Song, Mackenzie Wilkinson, Yasmin Padvan Hernandez, Junior Lara de Deus, Noel Mr. Wright, Mr. Karine Lama, Mr. Ser Faltin, Mr. Royal Gough, and Mr. Genevieve Stein O’Brien of John’s. Hopkins.

About this psychopharmacology and neuroscience research news

author: Fertilizer for roses
sauce: johns hopkins medicine
contact: Rose Doren – Johns Hopkins University School of Medicine
image: Image credited to Neuroscience News

Original research: closed access.
“Psychedelics restart the critical period of social reward learningby Gul Dolen et al. Nature

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overview

Psychedelics restart the critical period of social reward learning

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

Although these drugs have been used in both spiritual and medical settings for thousands of years, a number of recent clinical successes have sparked renewed interest in developing psychedelic therapies.

Nevertheless, a unifying mechanism that could explain these common phenomenological and therapeutic properties remains unclear.

Here we demonstrate in mice that the ability to resume the social reward learning critical period is a common property among psychedelic drugs. Notably, the time course of resumption of the critical period is proportional to the duration of acute subjective effects reported in humans.

Moreover, the ability to restore social reward learning in adulthood parallels the metaplastic reversal of oxytocin-mediated long-term depression in the nucleus accumbens.

Finally, the identification of genes that are differentially expressed in the ‘open’ and ‘closed’ states suggests that extracellular matrix remodeling is a common downstream mechanism underlying critical period reopening by psychedelic drugs. provide evidence that there is

Taken together, these results have important implications for the implementation of psychedelics in clinical settings and the design of novel compounds for the treatment of neuropsychiatric disorders.