Never make a decision on an empty stomach… or a full stomach…

You are hungry already and dinner is hours away.  You’re getting irritable and making stupid decisions that you normally wouldn’t.  Or maybe you just had a big meal and you’re sated.  Your friend who is seated next to you turns and asks for a favor; you pleasantly agree and sink into your chair sleepily.  What’s going on?

An underappreciated fact about the neuromodulatory system is that release of these molecules can have diffuse and widespread effects all across the brain.  Take dopamine and leptin. Dopamine is a chemical that drives decision-making – among other things, but it really does have an important role in this – while leptin is generally thought to signal satiety.  Leptin is released from the fat cells of the body and we typically think of it acting on the hypothalamus, an area responsible for many metabolic behaviors.  When more leptin is circulating in the blood stream, you will eat less food and increase more energy which makes it a natural candidate for yet another failed diet pill.  Since leptin interacts with motivation to eat food, an alternative set of areas it could interact with are the dopamine regions .  And in those regions, in the striatum in particular, the response to food and food pictures will be reduced when there is increased leptin.

It would be nice to know mechanistically how the two systems interact.  One method of going about this is to activate dopamine release through a stress pathway: by keeping pain at a constant self-reported score, a robust and constant amount of dopamine will be released.  Yes, for some reason people actually volunteer for these experiments.  Now we can exploit the fact that there are known variants in the gene responsible for leptin, LEP.  If you look at how people with these variants respond, you get large differences in dopamine release, which seems to preferentially effect the D2/3 receptors.  Although different researchers seem to disagree on which specific regions of the striatum are modified by leptin, a good guess it that this is highly dependent on the task and leptin will change the amount of dopamine available to the areas.

What affect might this have on behavior?  One behavior that these D2/3 receptors are involved in is risky decision-making.  We all have our own preferences for risky bets.  Some people prefer small bets that they are guaranteed whereas others prefer the risky option (these are the compulsive gamblers).  But it’s a bit more complicated than that.  Sure, you’d take a risky bet when the option was between a sure 5 cents and a “risky” $1.  But maybe you wouldn’t if you were guaranteed $100 with a risky option of $2000 or nothing.  How sensitive you are to these bets turns out to rely on the concentration of D2/3 receptors in the dorsal striatum.  Putting two and two together, we can bet that the leptin that has an effect on dopamine levels also has an effect on how willing you are to take a risk as the stakes get larger.

This means that all of our body is linked, together, with the state of the world.  Periods of hunger or bounty will cause people to behave in very different ways, with behavior linked to the body’s hormone signaling.  Particularly prevalent here is that hormones that are generally thought of as responding purely to food may have a broader role in signaling to the body how to properly respond to all sorts of situations.

References

Burghardt, P., Love, T., Stohler, C., Hodgkinson, C., Shen, P., Enoch, M., Goldman, D., & Zubieta, J. (2012). Leptin Regulates Dopamine Responses to Sustained Stress in Humans Journal of Neuroscience, 32 (44), 15369-15376 DOI: 10.1523/JNEUROSCI.2521-12.2012

Cocker, P., Dinelle, K., Kornelson, R., Sossi, V., & Winstanley, C. (2012). Irrational Choice under Uncertainty Correlates with Lower Striatal D2/3 Receptor Binding in Rats Journal of Neuroscience, 32 (44), 15450-15457 DOI: 10.1523/JNEUROSCI.0626-12.2012

Dunn, J., Kessler, R., Feurer, I., Volkow, N., Patterson, B., Ansari, M., Li, R., Marks-Shulman, P., & Abumrad, N. (2012). Relationship of Dopamine Type 2 Receptor Binding Potential With Fasting Neuroendocrine Hormones and Insulin Sensitivity in Human Obesity Diabetes Care, 35 (5), 1105-1111 DOI: 10.2337/dc11-2250

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