When you stay up all night, you might have felt tired but strangely energetic. Researchers at Northwestern University have figured out why this happens. They did a study on mice where they kept them awake for a short time. They found that during this sleep deprivation, the brain released more dopamine, which made the mice feel happy and rewired their brains to stay in a good mood for a few days.
These discoveries help scientists understand how moods change on their own. They might also provide insights into how quick-acting antidepressants, such as ketamine, function and reveal new targets for future antidepressant drugs. The study will be available online on November 2 in the Neuron journal, with Mingzheng Wu as the first author and Professor Yevgenia Kozorovitskiy as the corresponding author.
Kozorovitskiy said, “Chronic sleep loss is well studied, and its uniformly detrimental effects are widely documented. But brief sleep loss — like the equivalent of a student pulling an all-nighter before an exam — is less understood. We found that sleep loss induces a potent antidepressant effect and rewires the brain. This is an important reminder of how our casual activities, such as a sleepless night, can fundamentally alter the brain in as little as a few hours.”
Kozorovitskiy is an expert in neuroplasticity and holds a position as an associate professor of neurobiology and the Irving M. Klotz Professor at Northwestern’s Weinberg College of Arts and Sciences.
Changes in mood due to lack of sleep have been known to scientists for a while. For instance, disruptions in sleep and daily rhythms can sometimes trigger mania or temporarily relieve depression in patients. “Interestingly, the mood changes caused by short-term sleep loss feel very real, even in healthy individuals like myself and many others,” explained Wu, a researcher. “But we didn’t fully understand how these effects happened in the brain until now.”
To understand these processes, Kozorovitskiy and her team created a gentle experiment using mice without genetic links to human mood disorders. They aimed to induce mild sleep loss without causing significant stress to the mice, just enough to keep them awake. After a sleepless night, the mice became more aggressive, hyperactive, and hypersexual compared to those who had a regular night’s sleep.
The researchers used special tools to track the activity of dopamine neurons in the brain, which are responsible for the feeling of reward. They discovered that the dopamine activity increased during the short sleepless period.
Kozorovitskiy explained, “We were interested in discovering which specific brain parts were causing these behavioral changes. We wanted to know if it was a widespread signal affecting the whole brain or something more specific.”
Kozorovitskiy and her team studied four brain regions responsible for releasing dopamine: the prefrontal cortex, nucleus accumbens, hypothalamus, and dorsal striatum. After observing these areas for dopamine release during sleep deprivation, they found that three of the four regions (prefrontal cortex, nucleus accumbens, and hypothalamus) were involved.
To narrow down the results, they selectively stopped the dopamine reactions. The antidepressant effect vanished only when they silenced dopamine in the prefrontal cortex. On the other hand, the nucleus accumbens and hypothalamus seemed more connected to hyperactivity behaviors but less related to the antidepressant effect.
Kozorovitskiy stated, “The antidepressant effect remained, except when we muted the dopamine response in the prefrontal cortex. This suggests that the prefrontal cortex is a vital area to consider for therapy. It also emphasizes the idea gaining traction in the field: Dopamine neurons have different and important roles in the brain, not just predicting rewards.”
After a night of sleep deprivation, behaviors like hyperactivity and increased sexuality quickly returned to normal within a few hours. However, the improved mood or antidepressant effect lasted for several days. This indicated that there might be enhanced synaptic plasticity in the prefrontal cortex.
Upon closer examination, Kozorovitskiy and her team found that the neurons in the prefrontal cortex had small, flexible structures called dendritic spines. These spines can change in response to brain activity. When the researchers used a genetic tool to dismantle these synapses, it reversed the antidepressant effect.
Though the exact reasons aren’t entirely clear, Kozorovitskiy believes that evolution might have a role in this effect.
She explains, “Acute sleep deprivation seems to activate the body for a specific reason. Think of situations where there might be a predator or danger, and you need to stay alert and delay sleep. This could be what we’re observing. However, if you lose sleep regularly, it will have negative effects in the long run. But in the short term, being highly alert could be beneficial.”
Kozorovitskiy also advises against staying up all night to improve your mood. She notes, “The antidepressant effect is temporary, and we know the importance of a good night’s sleep. It’s better to exercise or go for a walk. This new information is more helpful in matching the right antidepressant for an individual.”
This study sheds light on the intriguing phenomenon of a single sleepless night’s ability to alleviate depression for several days quickly. It prompts further research into understanding the mechanisms underlying this effect, potentially offering new approaches to managing and treating depression.
Journal reference:
- Mingzheng Wu, Xin Zhang et al., Dopamine pathways mediating affective state transitions after sleep loss. Neuron. DOI: 10.1016/j.neuron.2023.10.002.