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PPeople who experience trauma often turn to treatment for help in adulthood, but persistent conditions such as PTSD can be difficult to treat. The adult brain, unfortunately, is not as open to change as it is to adolescence. New search published Wednesday in Naturehowever shows how the drug MDMA could reopen the door to the more open adolescent brain.
In the study, a team led by the neuroscientist Johns Hopkins University, Gül Dölen, showed that the effects of MDMA on the hormone oxytocin seemed to open a "critical period" in the brain of adolescent mice. This period requires a certain level of neuroplasticity, that is, an ability to reorganize neurons, which disappears when the brain reaches adulthood. The team suspects that this same neuroplasticity is at play in recent studies showing that MDMA can treat PTSD and other psychological disorders when used in combination with treatment.
In particular, the MDMA seems to open a critical period of rewarding social learning, a period of development in which one learns that it is nice to be a member of a group. As an adult, this critical period ends; it may be for this reason that the treatment of PTSD, which requires close social interaction with a therapist, is difficult – and seems to work best when MDMA is involved.
Discovering that mice were going through a critical period of learning the social reward was the first step in determining how to re-enter the adult man.
"The first thing that was really exciting and a big surprise was that there was a critical period where we could measure this social behavior in the mouse," says Dölen, the lab's principal investigator where the research was conducted. study was conducted. reverse.
"We believe that many brain diseases would be influenced by the existence of a critical period for rewarding social learning."
Discovering the "critical period"
Long recognized as a recreational drug, MDMA is experiencing a renaissance as a therapeutic drug for people with PTSD, as well as for autistic adults with social anxiety disorders. Several phases of FDA-approved clinical trials have shown that MDMA, when taken under the direction of a therapist and associated with multiple treatment sessions, provides rapid relief of stress symptoms. post-traumatic long after the effects of the drug faded. What remains uncertain is how MDMA actually affects the brain. Dölen's team suggested in the new study that the drug could work through the hormone oxytocin to promote plasticity in adults in the same way as in adolescent mice.
They tested this idea by first introducing 24-hour-old mice into two different enclosures, each with different types of litter. In one enclosure, the mice had the opportunity to go out with other mice and in the other, they were all alone. The idea was that they would become conditioned, by learning the social reward, to associate one type of bedding to friends and the other guy to social isolation.
After conditioning, the mice had free access to both bedding enclosures and the researchers observed how long the mice had spent in each of them.
It appeared that only adolescent mice (aged 42 to 98 days) were likely to learn by social reward, choosing to spend more time among the bedding that they associated with other mice. Adult mice, on the other hand, did not seem to internalize the association between bedding and camaraderie.
That's to say until they receive MDMA.
Reopen the door to plasticity with MDMA
After receiving MDMA – and then waiting for 48 hours for the drug to be eliminated from their system – adult mice learned to associate a litter type with the company, as did teenagers. This result demonstrates that MDMA not only has an effect on neuroplasticity but lasts long after the acute effects of the drug have subsided.
"It's about the long-term effects of the drug on the brain," says Dölen.
These results suggest that MDMA and other drugs like this could actually induce a state of child neuroplasticity, in which a person can relearn new behaviors – and unlearn old ones. This could be particularly important for humans suffering from psychological conditions that are difficult to treat throughout their lives.
Previous research had established that, in mice, oxytocin, a hormone, plays a crucial role in learning social reward by interacting with oxytocin receptors in the nucleus accumbens, part of the brain associated with the reward. In the new study, the team shows that MDMA can also activate these oxytocin receptors, apparently also opening the critical period during which reward social learning is possible.
When coupled with traditional therapies, Dölen suspects that MDMA may be the support that some people need to heal, especially if they do not feel relief through conventional psychotherapy.
"All those who have tried to treat brain disorders have had the spirit in the background that these things do not work as well as we would like because of critical periods of brain plasticity, but we do not have t had effective ways to reopen these windows, "says Dölen.
MDMA: Maybe not just for PTSD
Anthony Gabay, PhD, a postdoctoral fellow at Oxford University, did not participate in this study, but did research on the effects of MDMA on social behavior. He says reverse that this research adds valuable insights into the effects of MDMA on serotonin and oxytocin.
"The fact that the authors report context-specific effects reflects our own findings in humans: some of the social cognitive effects of MDMA depend on the context," he says. "As the authors note, MDMA being in phase 3 clinical trials, it is important to understand these mechanisms and to see how they could play a role in the therapeutic process."
In addition to the ongoing studies on PTSD, Dölen suspects MDMA of being an ally in the treatment of other psychological problems with social elements.
"The other major type of disease for which this would be important would be addiction, where the disease would not necessarily be caused by social behavior, but your ability to treat it potentially could be facilitated if the period of social behavior was open. "says Dölen. She mentioned 12-step recovery programs in which peer support is an essential part of healing, but early life experiences can make it difficult for members to connect.
"The link that must exist between the members of the group or between the patient and the psychiatrist could be stronger if this critical period could be reopened," explains Dölen.
Next, the team will work with other Johns Hopkins researchers to determine whether other systems in the human body are showing signs of critical periods and whether the idea of reopening critical periods can be generalized from a system to the next. other. It is important to note that studies such as this one can stimulate research into a drug that has long been considered strictly recreational.
Despite the long-standing reputation of the MDMA as a political party, Dölen warns, this study highlights the importance of its emotional and psychological effects.
"For people who use these drugs for recreational purposes, I think it's important to keep in mind that when you take them, they reopen a window of sensitivity. So you want to make sure you take them with people you trust, who are not going to take advantage of your sensitive state of mind and who will respect the tremendous opportunity and the potential impact of these drugs on your brain, " she says.
"These medications should not be taken without understanding the importance of what these medications are doing to you."
Abstract:
A critical period is a period of development during which the nervous system is expressly sensitive to the specific environmental stimuli needed for proper circuit organization and learning. Mechanistic characterization of critical periods revealed an important role for exuberant brain plasticity at early development and for the constraints imposed on these mechanisms as the brain matures. In disease states, the closure of critical periods limits the ability of the brain to adapt even when optimal conditions are restored. Thus, identifying manipulations that reopen critical periods has been a priority for translational neuroscience. Here we provide evidence that regulation of the development of synaptic plasticity mediated by oxytocin (long-term depression) in the nucleus accumbens constitutes a critical period for learning by social reward. In addition, we show that a single dose of (+/-) 3,4-methylendioxymethamphetamine (MDMA) reopens the critical period of social reward learning and leads to a metaplastic increase in long-term depression-dependent depression. oxytocin. The MDMA – induced reopening of this critical period requires the activation of oxytocin receptors in the nucleus accumbens and is recapitulated by stimulating the ends of oxytocin in the nucleus accumbens. These findings have important implications for understanding the pathogenesis of neurodevelopmental diseases characterized by social impairments and disorders that respond to social influence or result from social injury.
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