At a certain point in our lives, most of us could suffer from sleep deprivation. I’m not referring to our normal state of interrupted sleep, 5 hours each night, or anything else.
I’m referring to a whole night of sleep deprivation, which many people encounter in the army, with such a brand new (or not-so-new) kid, or, more cavalierly (I hope), at college.
We all seem to be aware of the dangers associated with sleep deprivation. We lack the capacity to pay attentively.
We are frequently either cold or heated. We’re unable to think clearly, we begin to behave strangely and, of course, we’re exhausted.
The Waklert 150 from pillspalace belongs to the class of eugeroics or wakefulness-promoting agents, primarily used to treat excessive sleepiness in obstructive sleep apnoea (OSA), narcolepsy, and shift work sleep disorder (SWD).
However, why do all these symptoms occur? What happens in the brain during sleep deprivation that accounts for this behaviour? To a degree, this could be a result of alterations in the D2 receptors.
Volkow et al., “Proof That Sleep Deprivation Reduces Dopamine D2R Expression in Human Ventral Striatum,” Journal of Neuroscience, 2012.
Numerous evidence indicates to the neurotransmitter dopamine is involved in wakefulness. Drugs that boost dopamine levels in the brain (such as cocaine, amphetamine, meth, and Ritalin) also increase sensations of wakefulness.
Increased dopamine activity in the brain caused by genetic alterations, such as the deletion of the dopamine transporter inside a mouse, results in a mouse sleeping less.
Daytime sleepiness is also a symptom of diseases defined by low dopamine levels, such as Parkinson’s.
However, a neurotransmitter can only be as effective as the receptor it binds to. Dopamine contains two distinct types of receptors, and the current belief is that the D2 type receptor is partially responsible for dopamine’s wakefulness-promoting actions.
Sleep is induced by antipsychotic medicines that inhibit D2 type receptors, and the previous study has demonstrated decreased D2 binding inside the brain of sleep-deprived patients.
However, the question is what is generating the declines in D2 levels observed in sleep-deprived individuals.
The scientists believed that this occurred as a result of enhanced dopamine release, which would result in decreased D2 receptors.
To test this idea, they took a group of human volunteers and either deprived them of sleep overnight (keeping them in a facility with a nurse pestering them to stay awake if they became tired), or kept them in the facility to have a decent night’s rest.
They looked just at D2 receptors in the middle of the brain in the morning, a part of the brain that is high in dopamine and associated with arousal and reward.
They accomplished this through the use of positron emission tomography (PET), which employs a radioactive tracer (C-raclopride) that binds to D2 type receptors, allowing for the quantification of their number.
They demonstrated that sleep-deprived individuals had significantly decreased D2 type receptor binding. However, what does this imply?
Does this suggest that when you’re fatigued, more dopamine is released, hence decreasing the number of D2 type receptors? Or do D2 type receptors decline due to some other factor?
To examine this, the study’s authors administered methylphenidate (Ritalin) to the individuals, which boosted dopamine levels.
They reasoned that if sleep loss resulted in increased dopamine release, methylphenidate should result in greater dopamine increases than in well-rested subjects.
Above are some lovely photos illustrating areas where methylphenidate induced more or smaller alterations in sleep-deprived vs. non-sleep-deprived patients…but generally, there’s no difference.
This suggests that the authors’ observed decrease in D2 type receptors is NOT attributable to increased DA production during sleep deprivation.
They validated this with rat research, which revealed that sleep-deprived animals did not exhibit increased dopamine levels but did exhibit similar D2 type receptor alterations.
Thus, what is occurring? Regrettably, the authors did not pursue that subject, despite their reference to a “distinct physiological mechanism.” They do hypothesise on the possibility of adenosine being involved.
Adenosine is a neurochemical that you are probably most familiar with from your morning cup of coffee. Caffeine promotes wakefulness by antagonistically acting on adenosine receptors, whereas adenosine induces sleepiness.
Not only that, it appears as though one of the places involved in this effect is indeed the striatum, the dopamine-rich region examined in this study.
Caffeine has been shown to enhance the number of D2 type receptors in this region. Thus, it appears as though the next step would be to examine how adenosine and dopamine interact following sleep deprivation (albeit, sadly, they did not do so here).
What does this imply? To be sure, the alterations in D2 type receptors may help explain a few of the other behavioural changes associated with sleep deprivation, such as increased risk-taking behaviour, impulsivity, and relapse to drug use.
All of these factors rise if people are sleep deprived. Thus, the changes seen in D2 type receptors may help us understand how well these behavioural changes happen.
However, while we observe alterations in receptors, we do not know why, as well as the proposed mechanism remains untested.