Northwestern University scientists may have figured out why pulling an all-nighter can leave us feeling loopy and downright giddy for days after. In a new study out this week, the researchers found that acute sleep deprivation in mice can trigger a rapid release of dopamine within the brain and boost its plasticity, temporarily creating hyperactive and antidepressant effects. The findings might actually help scientists learn how to craft better treatments for mood disorders, the authors say.
The researchers weren’t initially planning to look at how all-nighters can affect the brain, according to corresponding author Yevgenia Kozorovitskiy, an associate professor of neurobiology at Northwestern. “We came to this topic completely from an outsider perspective, thinking about how different experiences affect mood and mood stability,” Kozorovitskiy told Gizmodo in an email.
The authors, led by Northwestern postdoctoral fellow Mingzheng Wu, were actually interested in studying how the brain’s pathways related to dopamine —an important neurotransmitter that plays a role in many aspects of our biology, including mood—can change for the worse as we develop mood disorders like depression, and then rapidly change back in response to certain antidepressants, particularly ketamine. Their earlier work had focused on depression specifically, but the authors also wanted to know if dopamine could be critical to the formation of mania and the high-energy mood swings that come with it.
“Since it is challenging to model mania behaviors in animal models, we brainstormed and wondered whether the proverbial ‘all-nighter’ could be a good model for a mild, brief mania-like, unstable mood state,” Kozorovitskiy said.
The team’s latest research, published Thursday in Neuron, set out to induce the typical college experience in lab mice. They kept their mice up for a night, and then studied their behavior and the activity of brain cells responsible for producing dopamine; they also used well-rested mice as a control group.
As anyone who’s stayed up late might understand, the sleepless mice became more aggressive, hyperactive, and even hypersexual than controls. Inside the mice’s brains, the authors found that dopamine-related activity spiked in three of the four relevant brain regions they were tracking: the prefrontal cortex, nucleus accumbens, and hypothalamus. But the dopamine boosts in these regions didn’t affect the mice all in the same way.
In later experiments, the researchers selectively silenced the dopamine response in each region before running the test and found that the nucleus accumbens and hypothalamus were most strongly associated with the hyperactivity effect of an all-nighter, while the prefrontal cortex was linked to the antidepressant effect. This suggests, as other research has, that dopamine’s influences on our behavior are complex and varied. They also found evidence of temporarily enhanced neuroplasticity—the brain’s ability to rewire itself and adapt as needed—within the prefrontal cortex. This plasticity might additionally help explain why the antidepressant effect of an all-nighter can last for several days.
“We think we have recapitulated that short-lived, high-energy, slightly loopy feeling and found important dopaminergic mechanisms that control different aspects of that vibe,” Kozorovitskiy said. “The major message of this research is to remember that even the casual choices we make in life have a dramatic (and quick!) impact on our brains.”
Of course, while all-nighters may initially leave us feeling on top of the world, they’re often followed by a deep crash soon enough. And chronically poor sleep may even raise our risk of developing mood disorders or worsen their symptoms. So the authors certainly aren’t recommending sleepless nights as a boon against depression. But the lessons learned from this and similar research could very well help us understand how to help people suffering from depression, bipolar disorders, and other mood-related conditions—a goal that the Northwestern team plans to keep pursuing.
“We want to understand the neuroscience of mood stability better, to ultimately open doors for better therapeutics that will help more people suffering from mood disorders,” said Kozorovitskiy.