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Are Oreos as addictive as cocaine?

If you've been on the Internet in the past week, chances are you've seen something about new research showing that Oreo cookies are just as addictive as cocaine. Is it true? 

Let's look at the source of all this buzz: a press release by behavioral neuroscientist Joseph Schroeder at Connecticut College. You can read it here: http://www.conncoll.edu/news/news-archive/2013/student-faculty-research-shows-oreos-are-just-as-addictive-as-drugs-in-lab-rats-.htm#.UmKURlCkquj 

First, it's just a press release. It hasn't been peer-reviewed or published. It hasn't even been presented in front of scientific peers at a conference yet (it will be at the Society for Neuroscience meeting next month). We don't have the complete details of the methods or results to fully scrutinize and draw conclusions from; we just have their brief descriptions of both to go off of.

Despite all of that, I think this is a really interesting study. I'm very (very) familiar with the methods they used due to my neuroscience degrees (and my first job post-grad school; whew, did I do a lot of immunohistochemistry staining for c-Fos!) Anyway, let's take a look at the 2 methods described: Conditioned Place Preference (CPP) and c-Fos immunohistochemistry (IHC) and what the results mean. 

Conditioned Place Preference

Conditioned Place Preference (CPP) is standard behavior test that's been used for decades to measure the rewarding or aversive nature of a stimulus -- most often a drug. CPP experiments are most frequently performed on rats or mice, and are done in specialized apparatuses that have two very distinct and recognizable chambers, either separated by a locking gate or connected by a third, small, neutral entry chamber (used for the test session described later).

The two chambers are outfitted in some way that makes them easily distinguishable from one another to a rat. For example, one may be painted with a high-contrast pattern (like checkerboard) and the other plain white or unpainted stainless steel; one may have a smooth floor and the other a fine mesh grid floor; one may have corncob bedding and the other pine, etc.

The training period takes several days. First, the animal is exposed to one stimulus in one compartment (the "place"). The next day, the same animal will be exposed to the control stimulus in the other compartment. This way, each animal learns to associate each compartment with a separate, distinct stimulus. Oreo cookies with compartment A and rice cakes with compartment B, for example. This is repeated for several days for each stimulus, so that the animals can form an association of place with each stimulus.

With food, the animals are allowed to eat while in the compartment. For drug vs saline injections, the animal receives the injection outside of the apparatus but then is immediately placed in the correct compartment.  

Oreos vs. Rice Cakes (not Oreos vs. Cocaine)

Okay, so now you have rats that are used to eating Oreos in chamber A and rice cakes in chamber B. How can you tell which experience is more rewarding (or less aversive)? You do a test session where you DON'T feed the rat anything and you place them in the neutral entry chamber (if your apparatus was built with one) and observe them for a few minutes to see if they spend more time in chamber A or chamber B. They will spend more time in the chamber that they associate with the more rewarding (or less aversive) stimulus. 

In addition to testing Oreos vs rice cakes, the researchers also had a group of rats that they tested CPP for after giving either an injection of a drug (either cocaine or morphine) or saline.

The press release doesn't specifically say that the rats spent significantly more time in the Oreo chamber vs the rice cake chamber; instead, it says: "the rats conditioned with Oreos spent as much time on the “drug” side of the maze as the rats conditioned with cocaine or morphine."  

The way I've been seeing this reported and discussed some places, you would think that the researchers did this: tested Oreos directly against cocaine by feeding rats Oreos in chamber A and injecting them with cocaine in chamber B, and then observed a place preference for the Oreo feeding chamber over cocaine. 

The way the findings of the CPP tests are worded in the press release aren't that ground-shaking, and are lacking some meaning since we don't have details about the control group. I can assume that the Oreo group was different from the rice cake group in a statistica lly significant way, but it's not stated in the press release. 


Immuno...what? Don't worry, I'll explain. Immunohistochemistry (IHC) is a type of tissue analysis that lets you visualize (either with a simple color stain OR pretty glowing fluorescent molecules) a specific antigen (a protein). This is accomplished by using antibodies (part of the immune system, hence "immuno") against the protein of interest. Antibodies are manufactured by injecting any one of many various species with the antigen  of interest and then taking a blood sample later to isolate the antibodies that their immune system produced against the antigen. 

There are two methods for IHC: direct and indirect. In direct IHC, the less common method, only one antibody (primary antibody) is used and it is labeled with an attached color that you can see under the microscope. In indirect IHC, a secondary antibody is used that is targeted against the primary antibody. So, you might have a primary antibody called "rabbit anti-c-Fos" which means it was produced in a rabbit and is specific for c-Fos and then you might have a secondary antibody called "goat anti-rabbit", which was produced in a goat and is specific for rabbit proteins and will thus attach to the primary antibody. Then, the color visualization will take place thanks to the secondary antibody, which can be labeled directly with a color or with certain chemicals that can undergo further reactions to produce color.

All those details don't matter terribly much, and have been described in much more detail elsewhere, if you are interested in really learning the nitty gritty details of how it works. Here's a cute video. Or, let me know and I can email you my protocols for performing IHC ;-) 

According to the press release, the protein that they stained for was c-Fos, which my first employer out of grad school memorably described to me as "the blood at the crime scene. It means you know something happened in that part of the brain." c-Fos is a marker for neuronal activity. The specific activity can't be determined with c-Fos alone -- you just know that the neurons were firing action potentials. Just like blood at a crime scene lets you know somebody was hurt, but not specifically how or why.  

For the IHC, they were interested in a specific region of the brain called the nucleus accumbens (NAcc), which you have probably heard referred to as the "pleasure center" of the brain.  They compared the brains of rats who were fed Oreos to the brains of rats who were injected with cocaine or morphine and they saw was significantly more c-Fos in the NAcc of the brains of rats fed Oreos compared to the brains of rats who received a cocaine injection. That is pretty interesting, but on its own is not sufficient evidence to support the headline "Oreos are more addictive than cocaine, study finds". 

Pleasure-seeking behavior in rats (and humans) is very complex, and involves much more than just the nucleus accumbens. The NAcc is part of a larger reward circuit that includes the amygdala, ventral tegmenal area, the septum, and the prefrontal cortex. There are two important neurotransmitters involved in this system: dopmaine and serotonin. Getting into the full details of the reward pathways of the brain is way beyond the scope of this article (I've got some textbooks with whole chapters devoted to it). I bring it up to point out the problem with trying to over-simplify behavior and addition, and with making definitive claims based on studies that only look at one small piece of a much larger picture.

Additional studies that could strengthen these findings would be to use more than one high-fat/high-sugar food. The researchers are assuming that that is the quality that makes Oreos preferred over rice cakes, but without testing other foods with different ingredients and flavors that are also high-fat/high-sugar, we can't be sure it isn't some other quality. It would also be very interesting to have information about neurotransmitter release in response to various foods vs. drugs, since with drug addiction you can see depletion of serotonin or dopamine. Can food do the same thing?

Is Food Addiction Real?

I think it's too soon to say that we have definitive, irrefutable, evidence that food addiction is real. Researchers have argued against the idea of food addiction for years, due to the fact that food is necessary for survival. They argue that it makes evolutionary sense for food to elicit pleasure in humans since we are required to eat to stay alive. I would be inclined to agree with this. However, I also find it interesting that the other behaviors that are associated with activation of the nucleus accumbens are all behaviors that have the potential to become addictions -- sex, gambling, drugs, alcohol. Therefore, I think it is probable that food could be added to the list, especially processed and refined foods. 

What do you think? 

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