When you wake up in the morning, you probably don’t always feel 100% on top of things. Besides feeling drowsy, you make decisions more slowly than you do when you are wide awake. Things are different! But maybe that cup of coffee will help you out…
What’s going on in your brain? It’s been known for a while that adenosine receptors are key to the whole caffeine-waking-you-up thing – caffeine binds one type of adenosine receptor – but there is something more going on. Volkow et al. had previously implicated a dopamine receptor as somehow changing in sleepy subjects. They measured receptor activity using a PET scan; this is a technique where a researcher injects a chemical into a subject that binds to specific receptors; when it is bound, it is detectable by the PET scanner. This binding might increase or decrease depending on the number of receptors (up- or down- regulation) or because the receptors are bound by other things – such different levels of dopamine itself binding the receptors.
Volkow et al. cruelly sleep deprived subjects in order to understand how dopamine was changing by using PET. What they found is that the longer you are awake, the less the dopamine receptors will bind. But this could either mean there is more dopamine in the system or that there are fewer dopamine receptors available to be bound. They also gave some of these subjects provigil, which acts on the dopamine reuptake transporters which carry the dopamine away; when blocked, the dopamine cannot be carried away very effectively and just hangs out, building up. If the change in binding was due to increased dopamine, the effect of provigil should be different for sleep-deprived subjects than for well-rested patients. Since this was not the case, Volkow et al. suggest that the number of receptors are themselves getting regulated (though I don’t understand why they don’t know that the dopamine transporters themselves can’t be being regulated instead?).
The receptors that they identified as being important are the D2-type dopamine receptors. There are many different types of dopamine receptors in the brain, and what exactly each of them is doing is a bit of a mystery. Broadly speaking, they can be divided into two classes: the D1-type and these D2-type receptors. D1-type receptors tend to be exciting to the cells in some sense, while the D2-type receptors are somehow inhibitory.
It turns out that D2-type receptors are regulated in other ways; for instance, social status can affect your D2 receptor level. Simply moving a monkey from living on its own to living in a group will change the receptor level depending on whether it is a high-status animal or a low-status one. In humans, individuals with low social support show low levels of D2 receptor binding while individuals with high social status show high levels of receptor binding. This is important for a variety of reasons; most importantly according to papers (ie, it gets the most funding from NIH), individuals with low social support (‘social status’) are most prone to cocaine addiction. This is true in humans, monkeys, rats, everything. Perhaps generalized stress results in low levels of D2 receptors? At the least, we can now all use this as an excuse as to why we make poor decisions when we’re sleepiest.
Volkow, N., Tomasi, D., Wang, G., Telang, F., Fowler, J., Logan, J., Benveniste, H., Kim, R., Thanos, P., & Ferre, S. (2012). Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain Journal of Neuroscience, 32 (19), 6711-6717 DOI: 10.1523/JNEUROSCI.0045-12.2012
Morgan, D., Grant, K., Gage, H., Mach, R., Kaplan, J., Prioleau, O., Nader, S., Buchheimer, N., Ehrenkaufer, R., & Nader, M. (2002). Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration Nature Neuroscience, 5 (2), 169-174 DOI: 10.1038/nn798