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EVANSTON, Ill. — Could pulling an all-nighter work better than taking an antidepressant? Occasionally skipping a night’s sleep can temporarily alleviate depression, a new study reveals. Researchers discovered that acute sleep loss enhances dopamine release, often dubbed the “love drug,” and literally rewires brain connections. This phenomenon might leave the body tired, but the mind experiences a “slap-happy” giddiness.

Now, neurobiologists at Northwestern University have unraveled the mechanisms behind this punch-drunk sensation. By inducing mild, acute sleep deprivation in mice and analyzing their behavior and brain activity, they noted an increase in dopamine release and heightened “synaptic plasticity” — the brain’s way of rewiring itself, which sustains this elevated mood for days.

Their findings could deepen our understanding of natural mood transitions and inform the development of fast-acting antidepressants, like ketamine, identifying new targets for these drugs.

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,” says Professor Yevgenia Kozorovitskiy, the study’s corresponding author, in a university release. “We found that sleep loss induces a potent antidepressant effect and rewires the brain.”

The team’s novel experiment on mice without genetic predispositions to human mood disorders reveals behavioral shifts towards aggression, hyperactivity, and increased sexuality after sleep deprivation. This was accompanied by heightened dopamine neuron activity.

“We were curious which specific regions of the brain were responsible for the behavioral changes. We wanted to know if it was a large, broadcast signal that affected the entire brain or if it was something more specialized,” Prof. Kozorovitskiy explains.

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The research focused on four brain regions responsible for dopamine release: the prefrontal cortex, nucleus accumbens, hypothalamus, and dorsal striatum. They found that three of these areas were involved after acute sleep loss. To refine their results further, the team selectively silenced dopamine responses, noting that the antidepressant effect vanished only when dopamine inputs in the medial prefrontal cortex were silenced.

“That means the prefrontal cortex is a clinically relevant area when searching for therapeutic targets. But it also reinforces the idea that has been building in the field recently: Dopamine neurons play very important but very different roles in the brain,” Prof. Kozorovitskiy states. “They are not just this monolithic population that simply predicts rewards.”

While behaviors like hyperactivity and heightened sexuality dissipated within hours after sleep deprivation, the antidepressant effect persisted for days, suggesting enhanced synaptic plasticity in the prefrontal cortex. This was confirmed when the team observed the formation of dendritic spines — dynamic structures that respond to brain activity — in individual neurons.

Disassembling these synapses using a genetic tool reversed the antidepressant effect.

“It’s clear that acute sleep deprivation is somehow activating to an organism. You can imagine certain situations where there is a predator or some sort of danger where you need a combination of relatively high function with an ability to delay sleep,” says Prof. Kozorovitskiy. “If you are losing sleep routinely, then different chronic effects set in that will be uniformly detrimental. But in a transient way, you can imagine situations where it’s beneficial to be intensely alert for a period of time.”

The researchers caution against using sleep deprivation as a mood enhancer.

“The antidepressant effect is transient, and we know the importance of a good night’s sleep. Rather than resorting to all-nighters, healthier alternatives like exercising or walking are advisable. I would say you are better off hitting the gym or going for a nice walk. This new knowledge is more important when it comes to matching a person with the right antidepressant,” Prof. Kozorovitskiy concludes.

The study is published in the journal Neuron.

Symptoms of Depression

Depression is a common and serious medical illness that negatively affects how you feel, the way you think, and how you act. It can lead to a variety of emotional and physical problems and can decrease your ability to function at work and at home.

The symptoms of depression vary from mild to severe and can include:

  • Feeling sad or having a depressed mood (This is the most common symptom of depression. It can feel like sadness, grief, emptiness, or hopelessness.)
  • Loss of interest or pleasure in activities once enjoyed
  • Changes in appetite or weight
  • Trouble sleeping or sleeping too much
  • Loss of energy or increased fatigue
  • Difficulty thinking, concentrating, and making decisions
  • Restlessness or feeling slowed down
  • Feelings of worthlessness or guilt
  • Thoughts of death or suicide

South West News Service writer Stephen Beech contributed to this report.

Lea la versión en español en EstudioRevela.com: Una noche sin dormir podría revelar una sorprendente cura para la depresión.

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