Dopamine and Obesity: The D2 Receptor

Apr 01 2010 Published by under Addiction, Behavioral Neuro

Sci would like to note that today's entry is being written on the adorably tiny screen of her netbook, which is named Ruby. Everyone say hi to Ruby!
Unfortunately, this is because her wireless on her normal computer suddenly decided that it was too good for her modem. Perhaps it's an April Fool's Day joke. This is not a good time for this to happen, but of course the not good times ARE the times when this happens, as we all know. And so, until that gets fixed, we are stuck on the netbook, which may mean increased typos and various other things that happen when Sci's hands are confined to a 10" space.
A few days ago Sci looked at a recent study which has come out on dopamine and obesity, which showed changes in reward-related behaviors and changes in the dopamine D2 receptor after rats got really fat. This paper (which apparently some people decided to interpret as "food is just like heroin", which is just silly) was based on the hypothesis that severe chronic overeating results in some changes in the brain which are similar to those seen in drug addiction.
Sci hasn't really looked into this before, but this really began to interest her. She decided to dig in a little, and take a look at some of the clinical literature, in particular some of the human stuff.
And so here we go. Wang et al. "Brain dopamine and obesity" The Lancet, 2001.

Now, as you'll know from my previous post, there are lots of possible variables involved in obesity in society, including food availability, physical exercise, etc. But there are a lot of OTHER variables that control food intake and overeating in an individual person. There are hormones such as leptin and ghrelin which control appetite, and other hormones and neurotransmitters like dopamine, serotonin, GABA, and norepinephrine, which control food intake through other mechanisms. Scientists think that dopamine, in particular, helps to regulate the pleasurable aspects of eating.
The previous post shed some light on the dopamine D2 receptor, which is actually a family of receptors in the dopamine system. To give you a little bit of background (if you want more, see the post on dopamine), dopamine is a signaling molecule known as a neurotransmitter, which is released from one neuron and binds to receptors on another neuron to produce effects. There are two major classes of receptors which bind dopamine (called dopamine receptors, obviously), the D1 like and the D2 like.
Both types of dopamine receptors are very important in addiction related stuff. Scientists have known for a long time that addictive drugs all affect dopamine levels in some way, and other more "natural" stimuli, like food and sex, also affect dopamine. Food, sex, and drugs (and who knows, possibly rock and roll. That would be a cool study) cause increases in dopamine in an area of the brain called the nucleus accumbens:

(say it with me "NUKE-LEE-US accumbens". I swear, if I hear another perfectly intelligent scientist say "nuke-u-lus"....)
And increases in dopamine in the nucleus accumbens are often associated with feelings of reward in response to these things. So when you eat something tasty, dopamine goes up, you feel good. When you take cocaine, dopamine goes WAY WAY up, and you feel REALLY REALLY GREAT. Until you don't.
And the dopamine receptors come in to this in different ways. Scientists have found, in particular, that levels of D2 receptors in your brain correlate pretty well with some aspects of drug taking. For example, cocaine addicts have lower D2 levels than non-cocaine addicts, and chronic exposure to drugs like cocaine can decrease D2 receptor levels. Cause and effect (or at least one very small cause and effect in what is a probably extremely complicated mechanism).
But the question is, if dopamine has a lot of do with rewarding responses to things, and drugs and natural rewards like food both stimulate dopamine, can drugs and food have some similar effects? For example, could someone who is a cocaine addict, and someone who is a severely chronic overeater have similar changes in the brain which may contribute to their overeating?
To test this, the Volkow lab (Dr. Nora Volkow is the current head of the National Institute on Drug Abuse, and does some really cool, incredibly wide ranging research in humans and animals on things like cocaine, psychiatric drugs like Ritalin, and things like obesity) took a group of obese people, and a group of people who were at normal weight. They checked both of these groups for D2 receptors using PET imaging.
PET imaging (positron emission tomography, but PET is a lot easier) is a technique that you can use in living humans and animals. Very, very basically, you give a very small amount of radioactive tracer linked to your drug of interest, which is usually a drug you want to bind to the receptors you're looking for. As that tiny readioactive tracer decays, it can be detected, and so where it binds can ALSO be detected. Don't worry, it's safe, the radioactive tracer is VERY tiny. Sci's done it and she's still not glowing green as far as she can tell.
In this study they looked at D2 receptors in the obese and non-obese patients. The hypothesis was that, if chronic overeating causes changes in the dopamine system which are similar to those seen with drugs of abuse, the D2 changes should be similar, and obese people should have LOWER D2 levels in reward-related brain areas. And that is in fact exactly what they saw (Sci would show you a pic, but Ruby doesn't do that right now).
This is a really small, pretty preliminary study, and a lot of work has been done since then. For example, this study didn't examine whether obese patients have different reward-related responses to food (it turns out they do), and whether they respond different to drugs of abuse (I don't know if this has been done yet). Also, these studies are often very difficult to do in humans. The patients may be obese, but does that necessarily mean that they are chronic overeaters? Does that necessarily mean they have a big problem with food? Sci thinks it might be better to look at obese people who have repeatedly tried and failed to decrease their eating and to lose weight if you want to start looking for chronic overeating as an addiction, and compare those people to other obese people and non-obese people to see how their reward-related responses differ. And who knows, it's very possible that people are working on this right now!
WANG, G., VOLKOW, N., LOGAN, J., PAPPAS, N., WONG, C., ZHU, W., NETUSLL, N., & FOWLER, J. (2001). Brain dopamine and obesity The Lancet, 357 (9253), 354-357 DOI: 10.1016/S0140-6736(00)03643-6

6 responses so far

  • Jason says:

    The good news (well, "good" in some sense) is that binge eating is finally being considered for inclusion as a unique diagnostic category in the DSM-V. I wonder if this type of obesity can be considered a chronic form of binge eating disorder.

  • becca says:

    Are there any polymorphisms in the D2 receptor? Or any associated proteins?
    I was just wondering if different affinity per receptor could impact the in vivo imaging.

  • Pietr Hitzig says:

    David Comings has maintained that D2R polymorphism is critical.

  • Tybo says:

    ^ Since that 1991 paper, most of the DRD2 lit I've come across has been linking it to sensation-seeking behavior.

  • AK says:

    I'd certainly say my own (somewhat minor) eating problems count as "sensation-seeking". The specific sensation of chewing and swallowing pleasurable food (good-tasting and well supplied with protein and fat) combined with the stretching of my stomach provides a burst of pleasure (with every swallow) reminiscent of that when I successfully solve a problem, receive an accolade, or achieve some other success. I would suspect a neural linkage between such sensations and the stimulation of the "pleasure center"* (remembering what an oversimplification the whole "pleasure center" thing is), perhaps combined with endocrine linkages.
    I would also suspect a case of "habituation" where the reduction in receptor density is linked to overstimulation at some point in the chain, a typical negative-feedback process found widely within the neural system.
    A speculation I find persuasive is that a particularly strong linkage between stomach stretching and stimulation of the "pleasure center" is a major contributor to binge eating (and perhaps over-eating in general). Remembering, of course, that a variety of complex linkages are involved, some of them neural and some endocrine.
    A quick search found little research in this direction, the closest (and it's not very) being "Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects" and a few references therein.
    * Obviously "stimulation of the pleasure center" is simplistic to the point of gross distortion. But so is any discussion of dopamine (or any neurotransmitter/neurohormone) in a particular region of the brain: the specific function of such a chemical depends on the specific functions of the neuron(s) releasing it and those receiving it. Thus "Cause and effect (or at least one very small cause and effect in what is a probably extremely complicated mechanism)" in the main article.

  • Marnia says:

    I'm curious whether this same phenomenon is at work in compulsive porn use. Super-stimulating food dampened the rats' pleasure response...driving them to seek (and seek) for satisfaction by binging.
    Both sex and food are natural reinforcers, and both are apparently governed by the striatum (where the D2 receptors in the study dropped).
    It may be that super-potent sexual stimuli also cause a drop in pleasure and D2 receptors, which drive binging on porn. For more, see: