Ecstasy may reopen brain’s ‘critical period’ to treat PTSD

(Credit: Getty Images)

The psychedelic drug MDMA reopens a “critical period,” when the brain is sensitive to learning the reward value of social behaviors, according to a new study with mice.

The findings may explain why the drug may help treat people with post-traumatic stress disorder (PTSD).

Scientists first described critical periods in the 1930s using snow geese. About 24 hours after a gosling hatches, if it can’t find its mother, it will bond with an object, even a non-living one. But, if the mother disappears 48 hours after her gosling hatches, the critical period is over, and the hatchling won’t bond.

There is evidence for critical periods that pave the way for development of language, touch, and vision in humans too.

“We wanted to know if there was a critical period for learning social reward behaviors, and if so could we reopen it using MDMA, since this drug is well-known to have prosocial effects,” says neuroscientist Gül Dölen, assistant professor of neuroscience at Johns Hopkins University School of Medicine.

Gathering spots

For the new study, which appears in Nature, researchers studied groups of mice in enclosures with different bedding. They put several mice together in one enclosure with one type of bedding for 24 hours and, in the next 24 hours, put the same mice alone in another enclosure with a different type of bedding.

The mice began to associate certain types of bedding with isolation or companionship. Then, they let the mice wander between enclosures with the two types of bedding and tracked how long the mice spent in each enclosure. The more time the mice spent in the bedding linked to their companions indicated more social reward learning.

“It’s why people gather around the water cooler,” Dölen says. They know it’s an optimal place to chitchat with companions.

In their experiments, Dölen and her colleagues found that the critical period for social reward learning in mice shows up around puberty and wanes once they become mature adults.

To see if they could reopen the critical period, the scientists gave MDMA to mature mice, waited 48 hours for the drug to wash out of their system, and observed how the mice explored their enclosure and behaved with other mice in the enclosure.

Following the treatment with MDMA, most of the animals responded to social interactions the same way as juveniles, by forming a positive association between social interactions and the bedding. This effect lasted for at least two weeks after the MDMA treatment. Mice given saline injections didn’t behave the same way.

“This suggests that we’ve reopened a critical period in mice, giving them the ability to learn social reward behaviors at a time when they are less inclined to engage in these behaviors,” Dölen says.

The researchers also observed that MDMA works to reopen the critical period only if mice get the drug when they are with other mice and not when alone. This suggests that using MDMA may depend on whether the animals are in a social setting, the scientists say.

Oxytocin response

The mice maintained their ability to learn the rewards of social behavior for up to two weeks after scientists gave them MDMA. The brains of the mice also had corresponding responses to oxytocin, a hormone made in the hypothalamus that acts as a signal between neurons that encode information about social rewards.

They found these responses by looking more closely at synapses, the spaces between brain cells called neurons. The researchers’ experiments showed that in mature mice they gave MDMA, oxytocin triggered signaling in the synapses that encode learning and memory, which does not typically happen in mature mice.

Opening the critical window for social reward behavior may also have implications for treating psychiatric conditions. A strong bond between a psychotherapist and patient is well-known to be important for successful treatment.

If MDMA reopens the critical period for social reward learning in humans in the same way it does for mice, then it could explain why the drug has successfully treated people with PTSD, perhaps through strengthening the psychotherapist-patient bond.

The US Food and Drug Administration has designated MDMA a “breakthrough therapy” for PTSD, meaning that the agency will fast-track the development and review of clinical trials to test it. However, the researchers caution that MDMA may not work for every psychiatric condition linked to social behaviors.

“As we develop new therapies or determine when to give these therapies, it’s critical to know the biological mechanism on which they act,” says Dölen.

Additional coauthors are from Johns Hopkins and MIT. The Kinship Foundation, Hartwell Foundation, Klingenstein-Simons Foundation, the National Institutes of Health, the New York Stem Cell Foundation-Robertson Award, and the National Institutes of Health Director’s Pioneer Award funded the work.

Source: Johns Hopkins University