Friday September 21 2012
The rats were allowed to eat as many M&Ms as they wanted
“Chocolate can create same high as opium,” reports the Daily Mail. It goes on to report that his research “found amazing comparisons between obese people and drug addicts”.
You’d be forgiven for thinking this was a study in obese people or drug addicts, when in fact the science behind this headline involved rats eating M&Ms.
The study found that a natural brain chemical called enkephalin – which has a similar effect to opium (the ‘active ingredient’ in heroin) – surged as rats began to eat M&M chocolates.
They also found that injecting a synthetic opiate, similar to enkephalin, into a specific area of the brain (the dorsal neostriatum) triggered a feeding frenzy in the rats.
They ate up to 5% of their body weight – the equivalent for an average human would be 3.6 kilos of M&Ms – the same weight in chocolate as three and a half bags of sugar.
The researchers also checked for clues that the rats were ‘enjoying’ their feed (such as licking their lips). They found that the rats did not appear to be enjoying it.
Many people with compulsive eating disorders report that they also take little enjoyment from binge eating, but found it very hard to stop.
The most important question to consider is how applicable this research is likely to be to humans.
While pure speculation at this point, the study raises the possibility that the dorsal neostriatum region of the brain (previously thought just to be associated with physical movement) may also be involved in addiction and compulsive eating.
It may be the case that some people are born with a ‘misfiring’ dorsal neostriatum that triggers a vicious circle of eating, leading to a surge in enkephalin, which leads to more eating, and so on…
However, these speculations are not backed up by this study, a great deal more research will be required to confirm, or disprove, this theory.
Where did the story come from?
The study was carried out by researchers from the University of Michigan and was funded by grants from the US National Institutes of Health.
The study was published in the peer-reviewed scientific journal Current Biology.
The media coverage focused on the link between the reported urge created by enkephalin in rats and what this might mean in humans, specifically obese people and drug addicts. However, the way the Mail’s headline was worded, and the start of the article, would lead many to believe that the research was actually performed on humans, rather than rats. It was only clear that the research was on rats further down in the body of the article.
Similarly, the link between this research and drug addicts was purely speculative, and was not in any way addressed by the rat study itself.
While it may be the case that the dorsal neostriatum region and/or enkephalin may play some sort of role in addictive and compulsive behaviours, this cannot be proved by the evidence provided by this study.
What kind of research was this?
This animal study used rats to investigate the effect of the brain chemical enkephalin on the motivation and urge to consume chocolates, specifically M&Ms.
Enkephalins are part of a category of natural brain chemical, called endorphins, that bind to receptors in the brain called opioid receptors. The opioid receptors are the main route for opiate drugs to exert their effects in the brain, including reducing pain and producing pleasurable feelings.
While used widely in the past as a painkiller, opiates are now usually reserved for the treatment of severe pain due to their potential to cause addiction.
The deeply addictive drug heroin is essentially a type of opiate that has been chemically treated to make it much stronger.
Animal studies are useful in exploring the effects of new chemicals and processes. Rats and other rodents are often used as they share many key anatomical and physiological characteristics with humans. However, the major limitation with this type of work is how applicable the findings will be to humans as the biology of rats and humans, while broadly similar in some areas, can vary significantly in other areas.
What did the research involve?
The research consisted of a series of three tests.
Firstly, the rats were given free access to M&Ms, which they proceeded to eat for around 20 minutes. During this time both the amount of M&Ms eaten, and the levels of enkephalin inside their brains was measured.
A related chemical called dynorphin was also measured as the researchers wanted to see if this would also be affected by the consumption of chocolate.
The researchers detected a sharp spike in enkephalin levels, which then gradually trailed off as the rats ate their fill.
Secondly, the researchers injected a synthetic version of enkephalin into the dorsal neostriatum areas of the rats’ brains. This sent the rats into a compulsive pattern of eating so severe that the researchers had to remove the rats from the chocolate to stop them eating.
Finally, they performed a similar experiment, but carefully studied the rats to see if they were ‘enjoying’ their eating. There are a number of well-established signs that can show whether a rat is ‘happy’ with its food, such as licking its lips and sticking its tongue out of its mouth.
In the researchers’ opinion, the rats did not seem to be particualry happy during this episode of compulsive eating.
The analysis of the results presented by researchers was broadly appropriate.
What were the basic results?
When the rats were presented with M&Ms, they consumed approximately 10 M&Ms per 20 minutes (~10g). This caused an immediate peak in the levels of enkephalin in their brains, a 150% rise on their normal levels. Enkephalin levels remained elevated throughout the roughly 20-40 minute period during which each rat continued to eat, and then began to decline as the rats slowed and gradually ceased eating, typically returning back to baseline within the next 40 minutes.
In contrast to enkephalin levels, dynorphin levels failed to increase during eating, and instead remained unchanged throughout the meal.
When the researchers injected enkephalin directly into different areas of the brain to see if it stimulated intense eating habits, they found that the results varied depending on the precise area injected. Sites within the anteromedial quadrant of the dorsal neostriatum produced by far the most intense increases of more than 250%, compared to the normal intake of M&Ms. Most of the rats injected in these sites ate over 17g of M&Ms, equivalent to about 5% of their own body weight, which for rats is a massive amount.
The researchers usefully point out that this degree of elevated consumption (5% of body weight) is roughly proportional to a 68kg human consuming 3.6kg of M&Ms in a single hour, clearly overriding normal satiety signals (satiety is your body’s way of telling you that you have eaten far too much and that it is time to stop).
Being injected in this area also made the rats faster to begin eating, so not only were they being stimulated to 'eat more', they were also being stimulated to 'eat now'.
Further experiments were performed to assess whether the motivation generated by injecting enkephalin was a motivation to eat, or a motivation to seek the taste of sweet rewards. This involved studying the rodent’s faces and tongue protrusions for signals of liking M&Ms versus a sweet solution. These experiments concluded that the injection was making the rats 'want' to eat M&Ms more intensely, without making them 'like; sweetness any more in the sense of the taste.
How did the researchers interpret the results?
The authors conclude that their results show that “enkephalin surges” and “stimulation in the same anteromedial dorsal neostriatum region contribute to signalling the opportunity to eat a sensory reward and to causally generating increased consumption of that reward.” Furthermore, that the motivation triggered by this chemical release can more than double the amount of food the rats wanted to eat.
In the final paragraph of the discussion on the implications of their research, the authors of the study mention that this signalling system in rats “could in this way participate in normal motivations and perhaps even in generating intense pathological levels of motivation to over consume reward in binge eating disorders, drug addiction, and related compulsive pursuits”
This study in rats suggests that the action of the brain chemical enkephalin in the specific part of the brain called the anteromedial quadrant of the dorsal neostriatum is vitally important in signalling the desire to consume M&Ms. Additionally, that injecting artificially high levels of this chemical into this specific area of the brain can make the rats eat excessive amounts of M&Ms, in all likelihood overriding the effect of feeling full.
The media and researchers suggest that this chemical and signalling system may be involved in human conditions that generate harmful levels of motivation to over-consume, such as binge eating, drug addiction, and related compulsive pursuits.
However, this was purely speculative and from the researchers’ point of view was put in the context of what their results might mean in the grand scheme of things.
The researchers did not assert this claim with any certainty. The media angle, however, was less reserved, and phrases such as “amazing comparisons between obese people and drug addicts” are misleading and over-state the immediate implications of this research.
This research provides no direct evidence that this enkephalin signalling is involved in these conditions.
How applicable this research is to humans is a crucial first question. While rats are a useful first step in research terms, we cannot assume that the exact effects seen in rats will be replicated if similar experiments were done in humans. Research directly on humans would be the only way to accurately observe the effects.
Arguably it would be unethical to attempt to trigger the binge-eating of huge amounts of chocolate in humans (but it would be more healthy but possible equally unethical, if a way could be found to increase a person’s desire to eat leafy green vegetables or fresh fruit).
With that in mind, a further limitation of the study is that only chocolate, in the form of M&Ms, was studied. The effects of other types of food on enkephalin levels is uncertain.
However, this rat study is a useful first step to investigating the action of enkephalin in mammals.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.