Have you ever pulled an all-nighter and ended up feeling wired, hyper, even a little like you’re drunk? Well, scientists are trying to exploit this feeling to see if it could help people suffering from depression, and a new study in mice has discovered the changes in the sleep-deprived brain that seem to cause it.
For most of us, the thought of giving up a good night’s sleep is not a happy one. But, when they’re forced awake by a night shift, a long drive, or a last-minute study session, many people find that they feel surprisingly upbeat the next day. You might describe it as feeling “tired and wired,” or dizzy, or even a little delirious (but in a good way).
If just one night can have this kind of effect, the scientists reasoned, this could help us better understand how the brain changes to affect our mood, and how some antidepressants, like ketamine, can kick in so quickly.
“Interestingly, changes in mood after acute sleep loss feel so real, even in healthy subjects, as experienced by myself and many others,” said Mingzheng Wu, postdoctoral fellow at Northwestern University and lead author of a new study on sleep deprivation. a statement. “But the exact mechanisms in the brain that lead to these effects are poorly understood.”
To learn more, Wu and the team conducted experiments in healthy adult mice. They devised a system to keep the animals awake while minimizing the amount of stress they were under, using an enclosure with a raised platform above a slowly rotating beam. The mice could either rest on the platform, or go for an exploration below, but they had to keep moving to keep out of the path of the beam. The authors tested the device and found that when the mice were housed in it, they slept significantly less.
After a night of sleep deprivation, the authors observed the mice behaving more aggressively and hypersexualized. The culprit? Dopamine: the reward neurotransmitter.
The authors were able to see that dopamine signaling was increased in the animals’ brains, but they weren’t sure if it was specific to certain regions or a whole-brain effect. They looked more closely at four regions – the prefrontal cortex, nucleus accumbens, hypothalamus and dorsal striatum – monitoring for the release of dopamine and then silencing them one by one.
“The antidepressant effect persisted except when we silenced the dopamine inputs in the prefrontal cortex,” explained senior author Yevgenia Kozorovitskiy. “This means that the prefrontal cortex is a clinically relevant area when looking for therapeutic targets. But it also reinforces the idea that has been built in the field recently: dopamine neurons play very important, but very different roles in the brain. I’m not just this monolithic population that just predicts rewards.”
This point about therapeutic targets is key. According to the Centers for Disease Control and Prevention (CDC), depression affects 16 million American adults annually, and antidepressant medications are widely used. While some people have found traditional antidepressants to be transformative, they don’t work for everyone and can have significant side effects. Studies are exploring the potential of new approaches, such as psychedelics, for more difficult-to-treat cases, but there is still a need for better understanding that could lead to new therapies.
This is not to say, however, that Kozorovitskiy would recommend taking an all-nighter as a quick fix. Organisms may have evolved this state of heightened awareness for times when delaying sleep and being on high alert could protect them from predation and other threats, but over time, the problems of chronic sleep deprivation begin quickly. on top of these benefits.
It is, however, an important new path for researchers to continue to explore.
“We found that sleep loss induces a powerful antidepressant effect and rewires the brain,” said Kozorovitskiy. “This is an important reminder of how our casual activities, like a sleepless night, can fundamentally change the brain in just a few hours.”
The study is published in the journal Neuron.
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