All-nighter’s Antidepressant Effect: Sleep Deprivation Boosts Dopamine, Rewires Brain

Pulling an all-nighter beats the blues, according to a new study.

The occasional sleepless night – whether it’s revising or partying – can rapidly reverse depression for several days, say scientists.

They found that “acute” sleep loss increases the release of the love drug dopamine and rewires the brain.

Staying up all night can leave the body physically exhausted, but the brain often feels “slap-happy” and almost giddy.

Now, neurobiologists at Northwestern University have become the first to uncover what produces that “punch-drunk” effect.

Researchers induced mild, acute sleep deprivation in mice and then examined their behavior and brain activity.

Not only did dopamine release increase during the acute sleep loss period, but the team saw that “synaptic plasticity” was also enhanced – literally rewiring the brain to maintain the bubbly mood for the next few days.

They say their findings, published in the journal Neuron, could help scientists better understand how mood states transition naturally.

It also could lead to a more complete understanding of how fast-acting antidepressants – such as rave drug ketamine – work and help identify previously unknown targets for new antidepressant medications.

Study corresponding author Professor Yevgenia 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.”

First author Dr Mingzheng Wu said: “Interestingly, changes in mood state after acute sleep loss feel so real, even in healthy subjects, as experienced by myself and many others.

“But the exact mechanisms in the brain that lead to these effects have remained poorly understood.”

The team developed a new experiment to induce acute sleep loss in mice that did not have genetic predispositions related to human mood disorders.

After a sleepless night, the animals’ behavior shifted to become more aggressive, hyperactive and hypersexual, compared to controls that experienced a typical night’s sleep.

The researchers measured the activity of dopamine neurons, which are responsible for the brain’s reward response.

They found activity was higher in animals during the brief sleep loss period.

Kozorovitskiy said. “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.”

Kozorovitskiy and her team examined four regions of the brain responsible for dopamine release: the prefrontal cortex, nucleus accumbens, hypothalamus and dorsal striatum.

After monitoring these areas for dopamine release following acute sleep loss, the researchers discovered that three of the four areas – the prefrontal cortex, nucleus accumbens and hypothalamus – were involved.

However, the team wanted to narrow down the results even further, so they systematically silenced the dopamine reactions.

The antidepressant effect disappeared only when researchers silenced the dopamine response in the medial prefrontal cortex.

By contrast, the nucleus accumbens and hypothalamus appeared to be most involved in the hyperactivity behaviors but were less connected to the antidepressant effect.

Kozorovitskiy said: “The antidepressant effect persisted except when we silenced dopamine inputs in the prefrontal cortex.

“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.

“They are not just this monolithic population that simply predicts rewards.”

While most of the behaviors – including hyperactivity and increased sexuality – disappeared within a few hours following acute sleep loss, the antidepressant effect lingered for a few days.

That suggested that synaptic plasticity in the prefrontal cortex might be enhanced, say the researchers.

When Kozorovitskiy and her team examined individual neurons, they discovered just that.

The neurons in the prefrontal cortex form tiny protrusions called dendritic spines, highly plastic features that change in response to brain activity.

When the team used a genetically encoded tool to disassemble the synapses, it reversed the antidepressant effect.

While the team does not fully understand why sleep loss causes this effect in the brain, Kozorovitskiy suspects evolution is at play.

She said: “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.

“I think this could be something that we’re seeing here. 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.”

But Kozorovitskiy warned people not to start pulling all-nighters in order to brighten a blue mood.

She added: “The antidepressant effect is transient, and we know the importance of a good night’s sleep.

“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.’

Produced in association with SWNS Talker