Tag Archives: caffeine

Chill, it’s just coffee!

Dear friend,

As I wrap up my last week in Paris, I’ve started noticing a peculiar number of coffee shops at just about every corner. Usually filled with people enjoying pastries accompanied with a small coffee, these cafés represent a snapshot of Parisian life. Outside of the café’s, people typically sit at the small but cleverly ornamented tables calmly and almost elegantly sipping on their simple beverage while reading the newspaper or chatting with a friend.

Cafes paris

Its so easy to find a café in Paris! (photo courtesy of google maps)

This isn’t anything like back at Emory, though! Unlike the sleep deprived college students at Emory who drink coffee as on-the-go rocket fuel, Parisians especially savor their brewed drinks as a vital part of their day. Nobody’s running around, on the go, fumbling with their food and coffee on the train, or spilling their drinks as they rush among pedestrians. This honor rests almost exclusively with American tourists, and in fact, remains as one of my surefire methods to find and befriend Americans in Paris!

coffee

Coffee in Paris

I should mention that I personally don’t enjoy drinking coffee this way, or in any way for that matter. I find it far too bitter and it seems that even if I can gulp it down with heaps of added sugar, caffeine and I don’t get along very well. It all started back in middle school when I drank a giant bottle of Pepsi during a back-yard soccer game (This would be forbidden at Emory, a school renowned for only selling Coke products on campus!). After about 20 minutes I felt a burst of energy as I sprinted down the field, but my heart raced, and my face got incredibly warm. Panicking about my racing heart, I ended up going to the hospital after the game, only to have the doctors tell me I was fine. Of course, by the time I got there, the effects of the caffeine faded. Since that experience though, I try to stray away from caffeinated drinks because of the side effects that come with it.

Tired and hot after soccer

Tired and hot after caffeine and soccer (www.drdavidgeier.com)

 

However, I recently participated in a small group-experiment as part of a project for our class that involved drinking coffee. As a willing participant, I bought coffee from the local café at Cité Internationale, and quickly drank one cup before completing a series of reaction time tests to examine the effects of caffeine on reaction time.

The coffees we drank for our experiment!

The coffee we drank for our experiments!

 

My reaction time increased, but interestingly so did my perceived body temperature and alertness. This got me thinking about the effects of caffeine on the body. How does this drug, available so readily throughout most of the world, affect the brain and body? Once again, equipped with Neuroscience, I turned to the Internet in my search for answers.

It turns out that caffeine works by blocking the activation of brain processes responsible for regulating sleepiness and fatigue. These processes normally activate when a certain neurotransmitter, adenosine, binds to a certain receptor, the adenosine receptor. When awake, adenosine builds up in the body and eventually binds to its receptor, signaling the body to sleep. Caffeine also binds at this site, but it binds without activating fatiguing processes, and just gets in the way of adenosine binding. By doing so, caffeine keeps its users energized (Fredholm et al., 1999). Previous research also indicates that caffeine increases dopamine release in the striatum, and nucleus accumbens, areas of the brain responsible for motivation, reward, and sympathetic nervous system activities typically known as fight or flight systems (Balthazar et al., 2009).

antimicrobe.org
(antimicrobe.org)

In a recent study, Zheng et al. (2014) tested the effects of caffeine on temperature regulation and neurotransmitter release in the preoptic area and anterior hypothalamus (PO/AH) of the brain, areas responsible for regulating body temperature. According to their study, researchers chose to study these areas because increased dopamine activity here leads to a better tolerance for heat storage in the brain and facilitates an increased metabolic rate (Balthazar et al., 2009). To investigate whether caffeine helps produce these enhancing effects, researchers measured temperature, oxygen consumption, and neurotransmitter presence in rats during rest and exercise states. In a total of 10 male winstar rats, Zheng et al. (2014) measured baseline serotonin (5-HT), dopamine (DA), and noradrenaline (NA) release in PO/AH using a microdyalisis probe or cannula for control. This tiny filter collected neurotransmitters and allowed experimenters to analyze measurements. To further test for temperature and oxygen consumption, researchers measured core and tail skin temperature in the same spot for all rats, and oxygen with an oxygen/carbon dioxide measuring box. One hour before rats were placed in the box to run on a treadmill until fatigue at an 18m/min pace, investigators intraperitoneally injected (injected into the abdomen) rats with saline, 3mg/kg caffeine, or 10mg/kg caffeine. (See Link1 at the bottom for a video of rats running on a treadmill!)

(www.pt.kumc.edu:research:diabetes-research-lab:RatTreat01)
Oxygen/Carbon Dioxide measuring mechanism (www.pt.kumc.edu:research:diabetes-research-lab:RatTreat01)

From their data, Zhang et al. (2014) found that at rest, 3mg/kg caffeine levels did not result in any significant changes. However, at 10mg/kg, caffeine caused significantly higher core and tail temperatures, higher oxygen consumption, and extracellular DA and NA in the PO/AH. Data also showed that caffeinated rats showed increased endurance, and could run longer before fatigue set in. The researchers interpreted this to mean that caffeine facilitates dopamine pathways in the brain that lead to physical enhancements, specifically by modulating the PO/AH in a way that allows the brain to work under higher energy levels. I personally think of this as caffeine rearranging the brain’s thresholds for what we consider a state of exhaustion, and increasing energy consumptions by resetting the thermostat so we can function at a higher level. I  particularly chose this study  because the comprehensive testing used in the methods mimics these same high stress functioning levels I experienced while playing soccer.

I think as a whole the findings are incredibly interesting, and in my opinion, make perfect sense when interpreted this way. However I think that the researchers should definitely have included more details on the effect of caffeine on heart rate, as well as more incremental investigation on the effects of caffeine doses between 3 and 10 mg/kg. I would also like to see a larger sample size, or at least more than one trial per rat, as a sample size of 10 makes it difficult to collect meaningful data. I also wonder though, how long can this high energy state last before burning the body’s metaphorical engines? Perhaps future studies could test the effects of chronic caffeine use on prolonged energy levels.

As I continue my time in Paris, it feels great to see scientific explanations for everyday events. This past spring, I remember seeing a “contains caffeine” label on one of my running snacks when I ran a marathon. At the time, I thought that caffeine simply keeps you more awake, but little did I know that it facilitates increased endurance levels!

coffee chews
Caffeine chews

I’m glad neuroscience keeps sneaking up on me, pleasantly surprising me with answers. Who would have known that it would answer my childhood questions and help me chill out about coffee’s side effects.

For now, maybe coffee is not all that bad.

Here’s to new experiences and breaking out of my comfort zone!

Until next time,

Alex

 

References

Balthazar CH, Leite LHR, Rodrigues AG, Coimbra CC (2009) Performance-enhancing and thermoregulatory effects of intracerebroventricular dopamine in running rats. Pharmacol Biochem Behav 93:465–469

Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE (1999) Actions of Caffeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use. 51.

Zheng X, Takatsu S, Wang H, Hasegawa H (2014) Pharmacology , Biochemistry and Behavior Acute intraperitoneal injection of caffeine improves endurance exercise performance in association with increasing brain dopamine release during exercise. 122:136–143.

Link1: https://www.youtube.com/watch?v=PxH0SBjteuc

Café au Lait to get Through the Day

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.

Screen Shot 2015-06-22 at 1.43.12 PM

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

 

References:

Huang ZL, Urade Y, Hayaishi O (2011) The role of adenosine in the regulation of sleep. Curr Top Med Chem 11:1047–1057.

Lazarus M, Shen H-Y, Cherasse Y, Qu W-M, Huang Z-L, Bass C, Winsky-Sommerer R, Semba K, Fredholm B, Boison D, Hayaishi O, Urade Y, Chen J-F (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. The Journal of Neuroscience 31(27): 10067-10075

Confessions of a Coffee Addict

With the addition of new coffee vendors on Emory’s campus over the past three years, combined with the excellent surrounding breakfast hotspots, I have become one to regularly appreciate and truly enjoy a hot cup of coffee. Whether the coffee be from Starbucks, Rise-n-Dine or Dunkin Donuts, I am victim to daily expenditure at these vendors for my morning (and sometimes evening) caffeine fix. Now that my time in Paris is approaching its end, I will readily admit that I had routed the closest Starbucks locations to my dorm and to the building where we take classes (before my departure from New York). I saved those directions in my phone; anticipating daily visits to this familiar coffee shop.

My pre-departure routing of Starbucks to the Accent center (where we take classes)

When I realized that it would be a daily struggle to somehow go to Starbucks before my early morning class (thanks to the reliability of the French subway system), I decided to give the conveniently located French coffee (on campus) a chance. My first experience with French café was at the Cite Universitaire cafeteria, as I was presented with a Dixie-cup size equivalent cup of black coffee. No sugar, no milk…but I was pleasantly surprised. I didn’t realize how strong the coffee would be and I can safely say that 3 cups of the café coffee was overkill…

All throughout Paris, I have noticed that the café comes in one size: about a quarter of the size of the regular coffee we get back in America. The coffee is quite deceiving, as the small cup actually keeps me energized despite its miniscule volume. I quickly realized that coffee in itself is a part of French culture, as many cafes throughout the city orient their tables and chairs to face the streets—this way, people can enjoy a cup of coffee and “people watch”. I rarely see Parisians eating lavish breakfasts (doesn’t stop me though…); rather, they enjoy a simple black coffee with the morning paper. French culture, to me, seems to emphasize simplicity and reservation. A cup of coffee, then, serves as a means to collect your thoughts and appreciate the beauty of France while simultaneously obtaining a needed jolt of energy. A cup of coffee transcends the traditional role of a breakfast drink, as “une tasse de café” is readily available (and encouraged) at any time of day.

French breakfast at a local restaurant (notice the tiny coffee...)

One of the classes we are taking here is related to body enhancement and the new, innovative technologies that can alter normal human function. During class one day, Dr. Crutcher shared with us some research that suggested the caffeine fix from our morning cups of coffee actually yields some physiological effects besides just enhanced alertness. In the past, researchers found that caffeine can increase anxiety in the short run, but increased doses of caffeine over time (via more coffee, for example) can lead to a diminished effect because of the build up of tolerance (Rogers et al., 2010). Recent research suggests that caffeine, readily found in coffee, may modify the way the different brain areas react to social threats (Smith et al., 2012). What are the neurological implications of this? Smith et al. (2012) set out to determine if there really was a relationship between anxiety, threatening signals, caffeine and the brain.

How did they do this study? After obtaining a group of subjects, the researchers gave the participants in this study received a fixed amount of either caffeine or placebo in two different sessions. During each session, the participants were placed in an MRI machine that would give researchers an fMRI scan (functional magnetic resonance image). An fMRI is basically a way to measure the changes in blood flow in the brain. Changes in blood flow in the brain represent changes in activity and activation in the different areas of the brain. (For example, if an area of the brain is in use, then there is increased blood flow in that area.) While in the MRI machine, participants were asked to perform an “emotional face processing task” (EFPT). This task involved participants being presented with different faces, each representing different emotions, and they had to match the presented face to a target face at the top of the screen. (Similar to a matching game!) After seeing the faces and doing the matching task, the participants would rate their anxiety and mental alertness (compared to before the task) via a questionnaire. Researchers also measured their blood pressure (before and 2 hours after the treatment of either the placebo or caffeine) (Smith et al., 2012).

Turns out that when the participants who were administered caffeine saw the threatening faces, that is the angry and fearful faces during the EFPT, there was increased activation of a brain area called the “midbrain periaqueductal gray area” and decreased activation in another area called the “medial prefrontal cortex” compared to the placebo group (Smith et al., 2012). Participants who received the caffeine dosage had higher self-rated anxiety on the questionnaires and their diastolic blood pressures were higher also! However, the exact neural mechanisms and implications of how these areas actually process threatening images and scenarios are still unknown (Smith et al., 2012). So what was the point of this study then? Smith et al. (2012) suggest that these brain areas, that showed changes in activity, are actually related to social threat processing and anxiety in humans. Because there were actual changes in blood flow in these areas in response to threatening or anxiety-inducing faces, only in the light of a caffeine dosage, it seems to be that caffeine is modifying the patterns of activation in the brain. A daily dose of caffeine, in the form of coffee for most of us, then, can possibly affect the way we perceive threats and can possibly affect how anxious we are compared to when we do not consume caffeine.

Yum

As with almost everything that seems too good to be true, in this case a delicious cup of French coffee, this study seems to suggest that loading up on multiple cups of coffee a day might not be the best idea. But, I don’t really plan on giving up my black Americano any time soon (especially since I’m leaving France soon and am already having French coffee withdrawal).

-Noareen Ahmed

References:

Rogers, P, Hohoff C, Heatherley S  (2010) Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Neuropsychopharmacology 35: 1973–83.

Smith J, Lawrence D, Diukova A, Wise R, Rogers P (2012) Storm in a coffee cup: caffeine modifies brain activation to social signals of threat. Scan 7: 831-840