Most people who have ever pulled an all-nighter are familiar with this feeling of “exhaustion and overexcitement.” Although the body is extremely tired, the brain feels euphoric, dazed, and almost dizzy. Neurobiologists at Northwestern University were the first to discover what causes this “punch-drunk” effect. In a study, the researchers induced mild, acute sleep deprivation in mice and then examined their behavior and brain activity. During the acute sleep deprivation phase, not only did dopamine release increase, but synaptic plasticity also increased—literally rewiring the brain to maintain the exuberant mood for the next few days.

Signs of Sleep Deprivation

These findings could help researchers better understand how mood states transition naturally. They could also lead to a more comprehensive understanding of how fast-acting antidepressants (such as ketamine) work and help researchers identify previously unknown targets for new antidepressants. The research findings were published in the journal Neuron. Mingzheng Wu, a postdoctoral fellow at Northwestern University, is the first author of the study, and Professor Yevgenia Kozorovitskiy is the corresponding author.

“Chronic sleep deprivation is well researched, and its consistently harmful effects are well documented,” Kozorovitskiy said. “However, short-term sleep deprivation—such as when a student studies all night before an exam—is less well researched. We have found that sleep deprivation has a powerful antidepressant effect and rewires the brain. This is an important indication of how our everyday activities, such as a sleepless night, can fundamentally change the brain within a few hours.” Kozorovitskiy is an expert in neuroplasticity and an associate professor of neurobiology and Irving M. Klotz Professor at Northwestern University’s Weinberg College of Arts and Sciences.

A New Experiment

Scientists have long known that acute sleep disturbances are associated with altered mental states and behaviors. Changes in sleep and circadian rhythm in patients can, for example, trigger mania or occasionally reverse depressive episodes. “Interestingly, changes in mood after acute sleep deprivation feel as real to healthy subjects as they do to me and many others,” Wu said. But the exact mechanisms in the brain that lead to these effects are still poorly understood.

To investigate these mechanisms, Kozorovitskiy and her team developed a new experiment to induce acute sleep deprivation in mice that had no genetic predisposition to human mood disorders. The experimental setup had to be gentle enough not to cause significant stress to the animals, but just uncomfortable enough to prevent them from falling asleep. After a sleepless night, the animals’ behavior changed and they became more aggressive, hyperactive, and hypersexual compared to the control animals that had a normal night’s sleep.

Using optical and genetically encoded instruments, the researchers measured the activity of dopamine neurons, which are responsible for the brain’s reward response. They found that activity was higher in the animals during the short sleep deprivation phase. The researchers were curious to know which specific regions of the brain were responsible for the behavioral changes and wanted to know whether it was a large, broadcast signal that affected the entire brain or whether it was something more specific.

Increased Neuroplasticity

Kozorovitskiy and her team examined four regions of the brain responsible for dopamine release: the prefrontal cortex, the nucleus accumbens, the hypothalamus, and the dorsal striatum. After monitoring these areas for dopamine release following acute sleep deprivation, the researchers found that three of the four areas (the prefrontal cortex, the nucleus accumbens, and the hypothalamus) were involved. However, the team wanted to narrow down the results further and therefore systematically blocked the dopamine responses. The antidepressant effect disappeared only when the researchers blocked the dopamine response in the medial prefrontal cortex. In contrast, the nucleus accumbens and hypothalamus appeared to be most involved in hyperactive behavior but were less related to the antidepressant effect.

The antidepressant effect persisted unless we suppressed dopamine inputs in the prefrontal cortex. This means that the prefrontal cortex is a clinically relevant area in the search for therapeutic targets. But it also confirms the idea that has recently emerged in this field: dopamine neurons play very important but very different roles in the brain. They are not just a monolithic population that simply predicts rewards.

While most behaviors (such as hyperactivity and increased sexuality) disappeared within a few hours of acute sleep deprivation, the antidepressant effect persisted for several days. This suggested that synaptic plasticity in the prefrontal cortex may have been increased. When Kozorovitskiy and her team examined individual neurons, they found just that. The neurons in the prefrontal cortex formed tiny outgrowths called dendritic spines, highly plastic structures that change in response to brain activity. When the researchers used a genetically encoded tool to break down the synapses, the antidepressant effect was reversed.

A Development to Ward off Predators?

Although researchers do not yet fully understand why sleep deprivation causes this effect in the brain, Kozorovitskiy suspected that it was related to evolution. “It’s clear that acute sleep deprivation somehow activates an organism,” Kozorovitskiy said. “You can imagine certain situations where a predator or other danger is threatening and you need a combination of relatively high performance and the ability to delay sleep. I think that could be the case here. If you lose sleep regularly, various chronic effects occur that are consistently harmful. But temporarily, you can imagine situations where it is beneficial to be particularly alert for a certain period of time.” Kozorovitskiy also warns against staying up all night to chase away bad moods. “The antidepressant effect is temporary, and we know how important a good night’s sleep is,” she said. It is better to go to the gym or take a nice walk. In fact, sleep deprivation can have a negative impact on health, especially in the long term. The immune system is weakened, making you more susceptible to infections. At the same time, the risk of cardiovascular diseases such as high blood pressure, heart attack, and stroke increases because the body is under constant stress and inflammatory processes increase.

Sleepless Nights Can Endanger Heart Health

A poor night’s sleep can lead to an increase in blood pressure on the same night and the following day. Research published in the journal Psychosomatic Medicine provides a possible explanation for why sleep problems have been shown to increase the risk of heart attacks, strokes, and even deaths from cardiovascular disease. The link between poor sleep and cardiovascular problems is increasingly confirmed in the scientific literature, but the reasons for this link are not yet fully understood.

High blood pressure, medically known as hypertension, is a condition in which the pressure in the blood vessels is permanently too high. This forces the heart to work harder to pump blood through the body. High blood pressure often causes no obvious symptoms and goes unnoticed for a long time, but it can lead to serious health problems in the long term. High blood pressure puts strain on the heart and blood vessels, increases the risk of heart attack and stroke, and can also damage organs such as the kidneys and eyes. Since high blood pressure often goes unnoticed, it is important to have it checked regularly. A healthy lifestyle with sufficient exercise, a low-salt diet, and stress reduction can help lower blood pressure; in some cases, additional medication prescribed by a doctor is necessary.

Researchers at the University of Arizona wanted to learn more about how sleepless nights affect cardiovascular health and conducted a study of 300 men and women aged 21 to 70 with no history of heart problems. The participants wore portable blood pressure cuffs for two days. The cuffs randomly measured participants’ blood pressure at 45-minute intervals during the day and also during the night. At night, participants wore actigraphy monitors—wristwatch-like devices that measure movement—to determine their “sleep efficiency,” or the amount of time they spent in bed in deep sleep. Overall, those with lower sleep efficiency during this restless night showed an increase in blood pressure.

The next day, they also had higher systolic blood pressure—the upper number in a patient’s blood pressure reading. More research is needed to understand why poor sleep raises blood pressure and what this could mean in the long term for people with chronic sleep problems. Nevertheless, these latest findings could be an important piece of the puzzle in understanding how sleep affects overall cardiovascular health. Blood pressure is one of the best predictors of cardiovascular health. There are numerous publications showing that sleep has some influence on mortality and cardiovascular disease.