Have you ever pulled an all-nighter and ended up feeling stressed, hyper, even a little drunk? Well, scientists are trying to use that feeling to see if it can help people with depression, and new research in mice has revealed the changes in the sleep-deprived brain that appear to cause it.
For most of us, the thought of giving up a good night’s sleep is not a happy one. But when forced to wake up by a night shift, long commute, or last-minute studying, many people find that they feel surprisingly upbeat the next day. You might describe it as feeling “tired and stressed,” or dizzy, or even a little delirious (but in a good way).
If just one night can have this effect, the scientists say, it could help us better understand how the brain changes to affect our mood, and how some antidepressants, such as ketamine, can kick in so quickly.
“It’s interesting that mood changes after acute sleep loss seem so real even in healthy people, as I and many others have experienced,” said Mingchen Wu, a postdoctoral fellow at Northwestern University and first author of the new sleep deprivation study. statement. “But the exact brain mechanisms that lead to these effects are still poorly understood.”
To learn more, Wu and his team performed experiments on healthy adult mice. They devised a system to keep the animals awake while minimizing the amount of stress they experience, using an enclosure with a raised platform above a slowly rotating beam. Mice could either freeze on the platform or go explore below, but they had to keep moving to stay away from the beam. The authors tested the device and found that when mice were placed in it, they slept significantly less.
After a night of sleep deprivation, the authors observed more aggressive and hypersexual behavior in the mice. The guilty. Dopamine. reward neurotransmitter.
The authors could see increased dopamine signaling in the animals’ brains, but they weren’t sure if it was specific to certain regions or the whole brain. They took a closer look at four regions—the prefrontal cortex, nucleus accumbens, hypothalamus, and dorsal striatum—by monitoring their dopamine release and then silencing them one by one.
“The antidepressant effect was maintained, except when we silenced dopamine inputs in the prefrontal cortex,” explained senior author Evgenia Kozorovitsky. “This means that the prefrontal cortex is a clinically important area in the search for therapeutic targets. But it also reinforces an idea that has recently emerged in the field. dopamine neurons play very important but very different roles in the brain. They are 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 each year, 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. Research is exploring the potential of new approaches, such as psychiatric drugs, for the most difficult-to-treat cases, but there is always a need for improved understanding that could lead to new therapies.
However, that doesn’t mean Kozorowitzki would recommend pulling an all-nighter as a quick fix. Organisms may have evolved this state of heightened awareness for times when delayed sleep and heightened alertness can protect them from predators and other threats, but over time the problems of chronic sleep deprivation will quickly begin to outweigh these benefits.
However, it is an important new avenue for researchers to continue to explore.
“We found that sleep loss produces a powerful antidepressant effect and tunes up the brain,” Kozorowicki said. “This is an important reminder of how our casual activities, such as a sleepless night, can fundamentally change the brain in just a few hours.”
The research is published in the journal Neuron.
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