As all y’all know by now, I’m an experienced caffeine junkie. Currently, I’m trying to forgo it again (this Diet Coke right here is merely an aberration, do not look at the caffeine behind the curtain…). But really, it’s everywhere around us. Somehow I don’t think it was QUITE so prevalent until the age of Starbucks. but it seems like now you can’t go anywhere without running into a coffee shop or three. In some cities there is literally one on every street corner. And with the crazy lives we all appear to be living these days, shouldn’t we take whatever legal cognitive enhancement we can get our hands on?
And heck, with a Starbucks on every streetcorner, what’s a poor lady who is…*ahem*…increasing (for those not familiar with the Victorian term, it means preggers), to do? Some of us spend our lives pretty well addicted, but when a women in the US finds out she is pregnant, she is immediately to drop to no more than one caffeinated beverage a day. And 70{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} of expectant mothers apparently don’t even do that. So the big question is: is our children caffeinated?
Bjorklund et al. “Perinatal Caffeine, Acting on Maternal Adenosine A1 Receptors, Causes Long-Lasting Behavioral Changes in Mouse Offspring” PLoS ONE, 2008.
As a matter of interest, it turns out that people in most of the world consume about 76 mg of caffeine per person per day. In Finland and Sweden, for some reason, that number is more like 400 mg of caffeine. Any reason why? And I would be curious to know the rates for professors and grad students. I bet they’re closer to Finland.
I’m sure that many of you who have been pregnant have probably been told at some point that caffeine is not good for the baby. High caffeine intake has been associated with bad outcomes, and caffeine has been inplicated as a teratogen (a ‘teratogen’ is something that causes a birth defect). Of course since caffeine has been around for a while, lots of studies have been done, but often researchers use pretty high doses (more than 50 mg/kg, which is even higher than you’d see in Finland). So these researchers wanted to look at effects of lower doses of caffeine, and use a model that was a bit closer to the use you see “on the street”. So they took pregnant mice, and put the caffeine in their drinking water.
A note on caffeine: Caffeine is stimulant, but it’s not a psychostimulant like cocaine or Ritalin. Instead, caffeine acts as an antagonist at adenosine receptors. Adenosine is a nucleoside (which means that it has a molecule of adenine, like in DNA, with a sugar clinging on), and is generally an inhibitory neurotransmitter, which may be important in promoting sleep. Caffeine antagonizes, or inhibits the actions of adenosine, resulting in less promotion of sleep, and thus more wakefulness. So unlike cocaine, caffeine has no direct effects on the dopamine system (a system important in reward, and a system found to be in common with drugs that are abused). But don’t rule out those indirect effects. It turns out that caffeine has secondary effects on dopamine, because the adenosine and dopamine systems interact. So caffeine intake can produce small increases in dopamine (Fredholm, 1999). This is the first I’d heard of it, and I think I’m going to have to investigate.
Caffeine, like many drugs, has what we pharm people like to call a “biphasic effect”. At lower doses of caffeine (50-300mg, about what you’d get in 1-3 cups of coffee), caffeine acts as a stimulant, perking you up, and apparently giving you enhanced ability to concentrate and a feeling of well being (due to the dopaminergic interactions, apparently). At higher doses (300-800 mg, when you drink the whole pot of coffee) caffeine can make you nervous, shaky, and unable to sleep. When studying this in lab animals, you can’t really ask them about feelings of well-being or nerves, but it turns out that caffeine makes a good motor stimulant (like cocaine) at lower doses, while higher doses can induce things like seizures and stereotypies.
I should point out that caffeine doesn’t come close to cocaine in terms of addictive potential, though. First of all, it’s a lot less potent. “Low” doses of caffeine in rats would be something like 25 mg/kg, which, if you gave that dose of cocaine, would send the rat through the roof. So caffeine is a lot less potent. Secondly, the dopaminergic actions of caffeine are secondary to the adenosine reactions, and dopamine increases are much lower than anything you’d ever see with cocaine, even at the highest doses.
Ok, that was a bit of a long aside. But now you know.
Anyway, we’ve been testing the effects of drugs given to the mother on the babies for many many years, and it’s basically assumed that, if there are effects in the fetus, it’s due to the drug crossing the placenta and affecting the fetus itself. What’s crazy about this article is that they imply that it might be the effects of caffeine on the MOTHER influencing behavioral outcomes in the babies. And here’s how they did it.
They put caffeine in the drinking water of pregnant mice, titrating the dose to about the equivalent of 3-4 cups of coffee a day. Of course they had a group of pregnant mice that didn’t receive caffeine. They then took the OFFSPRING of those mice and ran them in locomotor activity tests (basically, put a mouse in a box. See how much it runs. Yay, you have data). It turns out that caffeine treated pups ran around a lot more than pups with no caffeine. Not only that, but when tested with cocaine, the caffeine treated pups proved more sensitive to the drug than the uncaffeinated pups (I have some small issue with that, but I’ll address that in the comments).
So they they looked at a new set of mice. These mice had been genetically altered to display low adenosine receptors, like someone would after prolonged exposure to caffeine (in other words, tolerance). These adenosine knockdown mice ALSO produced pups that were sensitized to caffeine and cocaine, just like the pups of mothers given caffeine. From this, the authors said that these sensitizing effects were due to the effects of caffeine on the mother, NOT the direct effects of caffeine on the pups.
And it gets better! They tested the GRANDCHILDREN of the caffeine treated mice, and found that they were also sensitized. Apparently this thing is all in the family.
Comments:
1) I really like the study over all, but I wonder about the effects that they got when they did a locomotor test following cocaine. I have given a LOT of cocaine to a lot of mice, and while their cocaine reaction in the caffeine treated mice looks good, the non-caffeinated mice barely show a blip. At 10 mg/kg cocaine (I assume it was given i.p., but I could be wrong), they should be seeing a nice significant increase in locomotor activity. Makes me wonder what their saline injection looked like.
2) Although the A1 knockdown mice (the ones with low levels of Adenosine receptors, like they had been drinking caffeine) produced pups that were sensitized like caffeinated pups, I’m not sure that this means that the mother’s adenosine receptor levels were to blame, even regardless of the genotypes of the pups. We know that adenosine has dopamine system interactions, and it could have been differential levels of dopamine, or another neurotransmitter affected by adenosine, that caused the changes. Furthermore, knockdown mice like these are born and raised this way, so you have to account for the effects of growing up with reduced adenosine receptors. So I think they might want to do adult knockdowns before they make a sweeping conclusion like this.
In general, I think this is a really neat study, though it’s certainly made me glad I’m drinking less caffeine than the Fins now. This has some pretty sweeping implications for things like hyperactivity in children, but I wouldn’t get all up in arms yet. Of course these are mice, not humans, and changes in adenosine receptors artifically could have difference consequences in humans than in mice. More investigation is obviously needed. But for you ladies out there who have one in the oven, you might want to pass up that diet coke. It might save you being a little frazzled by that locomotor stimulated child later.
Olga Björklund, Johan Kahlström, Peter Salmi, Bertil B. Fredholm (2008). Perinatal Caffeine, Acting on Maternal Adenosine A1 Receptors, Causes Long-Lasting Behavioral Changes in Mouse Offspring PLoS ONE, 3 (12) DOI: 10.1371/journal.pone.0003977
