My amazing “café au lait” from Coutume Café in the 7ème arrondissement
Who doesn’t love a nice, hot cup of coffee after a morning shower? Not only does it taste AMAZING, but it also wakes you up and gets you ready for the day to come. Every morning, for the last 4 or so years, I drink a cup of coffee while getting dressed or eating breakfast. So, upon coming to Paris, I undoubtedly continued my ritual.
The walk from Cité Universitaire (where I live) to Coutume Café (my favorite coffee shop).
I essentially used my love of coffee as an excuse to visit as many cafés and small restaurants as possible. However, I soon discovered the enormous difference between French coffee and the American coffee that I am used to. The French are huge advocates for espresso, that is, a coffee-like drink served in tiny porcelain cups. However, unlike American coffee, espresso is extremely potent and filled with a TON of caffeine. Over the past few weeks, I too have become a lover of espresso and the large amount of caffeine and “energy” that comes with it. However, I was not quite sure exactly how caffeine affects the brain resulting in what we perceive as a boost in energy and decrease in drowsiness. So, throughout my days in Paris, I looked for an answer.
Typical French coffee (left) vs. typical American coffee (right)
While searching for an answer, I stumbled upon an article by Lazarus et al. (2011) concerning the effects of caffeine on wakefulness. Previous research found that caffeine counteracts fatigue by binding to adenosine A2A receptors. Adenosine, an inhibitory neuromodulator, has been linked to regulation of the homeostatic sleep drive. So, by binding to the receptor in the brain that normally binds to adenosine, caffeine indirectly prevents adenosine from functioning properly, altering one’s sleep pattern (Huang et al., 2011). Lazarus et al. used this information to construct their experimentations.
In their study, Lazarus et al. bred a strain of rats that had a knockout of the A2A receptor in their nucleus accumbens, that is, these rats did not have this receptor within this specific brain region. They then performed EEG (electrical monitoring) tests on these rats and compared their electrical brain activity with that of control rats (rats that did not have the A2A knockout). The researchers administered equivalent concentrations of caffeine to both groups of rats and monitored their brain’s electrical activity during sleep cycles. What they found was extremely interesting. The caffeine caused increased wakefulness in the control rats (those that did not have the A2A receptor knockout), while caffeine had no effect on wakefulness in the experimental rats (those with the A2A receptor knockout). This means caffeine not only blocks adenosine from binding to the A2A receptor (Huang et al., 2011), but it also prevents the activation of the “adenosine break,” resulting in increased wakefulness.
A figure from Lazarus et al. (2011) depicting the adenosine A2A receptors in the nucleus accumbens of rat models. The left shows a control (wild-type) rat nucleus accumbens, while the right shows an experimental (knockout) rat nucleus accumbens.
Furthermore, the data from this study suggests that caffeine induces arousal and wakefulness by activating pathways in the nucleus accumbens that have formerly been associated with locomotion and motivational behaviors. This is a novel finding because it implicates caffeine in more than just the blocking of adenosine, but also in the activation of further neuronal circuitry, promoting a sense of “energy”.
A figure from Lazarus et al. showing the effect of caffeine on wakefulness. There is no significant increase in wakefulness in the A2A receptor knockout mice as more caffeine is administered. However, there is a significant increase in the wakefulness of wild-type mice as more caffeine is administered.
What I find super interesting about this study is how the researchers localized the antagonist effects of caffeine to the nucleus accumbems. In previous neuroscience classes, I learned of the association between the nucleus accumbens and cognitive processes such as motivation, pleasure and reward, thus implicating this brain region in numerous forms of addiction. With this in mind, I wish the experimenters had monitored the changes in behavior between the experimental and control rats when receiving differing levels of caffeine. This could be accomplished by using an intravenous self-administration task (IVSA). IVSA entails using chambers with small levers that, when pushed, cause specific drugs to be administered into the tail of that rat that pushed the lever (Figure 1). The researchers could perform IVSA for both control and experimental rats, and use either a saline or a caffeine solution as the respective drug. If this was done properly, I predict the control rats to show increased pushing of the lever when receiving caffeine compared to saline, corresponding to an greater feeling of pleasure and reward associated with the caffeine. Alternatively, I predict the experimental rats to show no significant difference in pushing of the lever between administrations of caffeine and saline because the caffeine does not affect their nucleus accumbens in the same way that it does for the control rats.
A very simplified version of the IVSA task in rat models.
Regardless, I find the study by Lazarus et al. to be extremely fascinating because, as a regular coffee drinker, it gives me insight to what is occurring in my brain!
Anyway, I’m about to go grab a coffee and walk around the city. Until next time!
~ Ethan Siegel
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