One of the interesting things that you get to see when you go to the Society for Neuroscience meeting is what’s up and coming, what’s hot, and what’s kind of fading from the forefront of the hivemind of neuroscience. As Sci walks around, seeing posters, hearing talks, seeing colleagues and friends, I hear words bandied around. Optogenetics is the new hotness. Oxytocin? A little last year.
And then there’s food and reward. It’s a quiet murmur, but it’s getting stronger. Things like “food addiction” and “sucrose reward” start to go around. And my ears perk up, because I personally find this subject FASCINATING. And you should, too. After all, there is a veritable symphony controlling what, and when, and how much you eat.
And to that symphony we can add the soft oboe modulating sound of the serotonin receptors in the nucleus accumbens.
Pratt et al. “Selective serotonin receptor stimulation of the medial nucleus accumbens alters appetitive motivation for sugar reinforcement within a progressive ratio task” Wake Forest University. 103.15.
Serotonin is such an amazing little molecule. It modulates so many things, but for all that, it has total, final control over almost nothing. Serotonin is found in the gut, in your heart, in your brain. It plays a role in pooping, in depression, in food, in temperature, in general mood, in visual processing, in libido. And now, in motivation for food intake.
While recent papers on food reward have focused on the hypothalamus, the Pratt lab have started to investigate the role of serotonin receptors in an area of the brain called the nucleus accumbens. Serotonin is the famous neurotransmitter that we all know and love, but remember that drug is only as good as its receptor. And serotonin has a LOT of receptors. Last I checked there were 14 established receptors, with at least three more suspected. But today we’re going to focus on five receptors, the 5-HT1a, the 5-HT1b, the 5-HT2c, the 5-HT6, and the 5-HT7.
And we’re focusing on a particular area of the brain, the nucleus accumbens, an area most famous for mediating the rewarding and reinforcing properties of…things. Like food. Sex. Drugs. You know, the basics. And of course, the area of the nucleus accumbens is full of different kinds of neurotransmitter receptors. Including those four serotonin receptors I mentioned above. And the question is, how much do these receptors affect motivation in a rat? Specifically, the motivation to…eat?
So the authors of this study looked particularly at how specific drugs which activate the 5-HT1A, 1B, 2C, 6, and 7 receptors changed rat motivation to get a delicious sucrose snack. And how do you measure motivation in a rat? In this case, the gold standard is the progressive ratio schedule. You take a rat, you put it in a box. You give it a lever, and you teach it that pressing the lever a certain number of times gets them a sucrose pellet. Then, you let him in there, and instead of pressing, say, three times, the rat (in this case) presses three times, gets a pellet, wants another, presses three times….and nothing. He has to press more. He has to press 6 times. Then 12 times. Then 24 times. Then 48 times…then…you get the idea. You can run this curve in humans as well, and after a while…it’s just not worth it. The point at which it’s just not worth it is called the breakpoint, and is used as a measure of how much motivation the rat has to achieve that particular reward. Once you know how much the rat’s willing to work, you can give different drugs to the rat, and see how they change the rat’s breakpoints, and thus the rat’s motivation to get those coveted sugar pellets.
So the authors of this study trained up these rats, and then did surgeries to be able to inject specific drugs for specific serotonin receptors, directly into the shell region of the nucleus accumbens. Then they looked at different doses of each receptor agonist, and watched the breakpoints.
They found that a 5-HT6 agonist injected into the nucleus accumbens shell INCREASED the breakpoints, increasing the rat’s motivation to get that sugar pellet. On the other hand, the 5-HT1/7 agonist (which in another poster was broken down into agonists for each specific receptor subtype, and it looks like 5-HT1A mediates the majority of the effect) reduces the motivation to get the sugar, reducing the amount the rats are willing to press. Finally, the 5-HT2C agonist…did nothing. Hey, it’s always good to have a negative control.
So what does this show? It shows that specific serotonin receptors in the nucleus accumbens shell change how motivated rats are to get the sugar pellet, and thus that serotonin receptors, in specific areas, can influence your food intake. The authors hypothesize that a balance between these receptors changes a rat’s motivation for tasty food. They hope that some day these findings can contribute to an understanding of problems like binge eating and uncontrollable food cravings, and help us learn the mechanism behind the symphony of chemicals that tell us what to eat, and when, and how much.