Why we do what we do

Stanford psychiatrist Neir Eshel discusses our misunderstanding of the brain's so-called "pleasure chemical" and asks us to consider the difference between 'liking' and 'wanting.'
Nicholas Weiler
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From Our Neurons to Yours Wu Tsai Neuro Podcast

Welcome to "From Our Neurons to Yours," from the Wu Tsai Neurosciences Institute at Stanford University. Each week, we bring you to the frontiers of brain science — to meet the scientists unlocking the mysteries of the mind and building the tools that will let us communicate better with our brains.



This week, we're tackling a BIG question in neuroscience: why do we do what we do?   

Specifically, we're talking about dopamine, and why the common understanding of this molecule as a "pleasure chemical" in the brain may be missing something fundamental.   

Join us as we explore the distinction between 'liking' and 'wanting', between reward and motivation, and how this could help us more deeply understand how dopamine shapes our behavior.  Tune in to gain insights into addiction, Parkinson's disease, depression and more.   

Don't miss out on this thought-provoking discussion with Neir Eshel, a psychiatrist and leading Stanford expert on dopamine and behavior. (Including a conversation about a recent paper published with Rob Malenka, who we spoke with back in our very first episode!)  
 

 

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Learn more

Eshel Lab website

Stanford Medicine study reveals why we value things more when they cost us more(Stanford Medicine, 2023)  

Striatal dopamine integrates cost, benefit, and motivation (Eshel et al., Neuron, 2024)  

The Economics of Dopamine Release (Stanford BioX Undergraduate Summer Research Program lecture)  

Youtube video of classic James Olds rat brain stimulation study

Episode Credits

This episode was produced by Michael Osborne at 14th Street Studios, with production assistance by Morgan Honaker. Our logo is by Aimee Garza. The show is hosted by Nicholas Weiler at Stanford's Wu Tsai Neurosciences Institute. 

If you're enjoying our show, please take a moment to give us a review on your podcast app of choice and share this episode with your friends. That's how we grow as a show and bring the stories of the frontiers of neuroscience to a wider audience. 


Episode Transcript

Nicholas Weiler: This is From Our Neurons to Yours from the Wu Tsai Neurosciences Institute at Stanford University. Each week we bring you to the frontiers of brain science to meet the scientists unlocking the mysteries of the mind and building the tools that will let us communicate better with our brains. Today, a very big question in neuroscience. Why do we do what we do?

 We tend to think of behavior in terms of reward and punishment. If you're trying to get a child to change their behavior, you offer a treat or a gold star for good behavior and a timeout for bad behavior. Now, if you've heard of any of the brain's chemical messengers, you've probably heard of dopamine. It's commonly thought of as the feel-good neurotransmitter. It seems to play a role in reinforcing behaviors that lead to rewards. And it's often discussed in the context of unhealthy behaviors like gambling, substance abuse, and even screen addiction. But what if our common thinking about dopamine is not quite right? What if it's not exactly tracking what gives us pleasure or reward per se, if it's not about what we like, but rather what we want, what we're motivated to work for? This distinction may seem subtle, but stick with me because thinking through this can lead us to a much deeper understanding of why we do what we do, and particularly why we often dislike some of our own behaviors, but keep doing them anyway.

 To give one example that helps to illustrate some of the complexities arising around dopamine, consider Parkinson's disease. People with Parkinson's often have tremendous difficulty with movement. Their movements get slow and it can be hard to initiate simple actions like walking through a doorway. But this disorder is caused by degeneration of the dopamine system. In addiction, which is linked to overstimulation of dopamine, it's easy to assume that the disorder has to do with pleasure and reward, but in Parkinson's disease this becomes murkier. What does a movement disorder have to do with the feel-good neurotransmitter? Or to put it another way, why is the same neurotransmitter deeply implicated in both addiction and Parkinson's, seemingly two completely unrelated conditions? This kind of discrepancy makes you wonder if the common understanding of dopamine is missing something fundamental. To dive into this topic and help us understand some of these subtleties, we spoke to Neir Eshel, a psychiatrist at Stanford who runs a lab studying dopamine and behavior.

 I'm really excited to talk today about the very fundamental question of why do we do what we do? One of the big players here is the neurotransmitter dopamine, that people think of it as being a pleasure chemical or a reward chemical. And I want to get into that in some depth in this episode, and you make a very interesting distinction between what we want and what we like. Can you tell us a little bit about that distinction? What's the difference between wanting and liking?

Neir Eshel: So when we think about how we interact with stimuli in the world, with objects around us, with people, with experiences, I like to separate that into two components of reward seeking. One is liking and one is wanting.

 Liking is the pleasure that we gain. It's how much a joy we get from it. Wanting is how much we're willing to work for it, how much effort we're willing to put in to achieve that reward. Oftentimes they go together, but there's lots of examples in which there are things that we want a lot that we actually don't like that much, and I see that dissociation in clinic pretty frequently. So addiction is a really classic example of this in which I have patients who come in who are addicted to a particular substance and they tell me, "I don't like it. I don't take this drug because it gives me a lot of pleasure, but I crave it. I need to have it. I'll do anything for it." And so when you think about that in the context of addiction, I think you can start thinking about all sorts of other examples too, in which the amount that you like something is not the same as the amount that you're willing to work for it or the amount that you want it.

Nicholas Weiler: Yeah, that makes a lot of sense. I think we all have things that we wish we did less of or wish we did more of. Exercise is good for us, but we don't always like it. I bite my nails. It's not something I enjoy doing, but it's something that I'm compelled to do. So how does dopamine help us understand this distinction?

Neir Eshel: There's been a hypothesis in the field for a while now that if you separate reward seeking into different components, for example, into wanting or liking, dopamine might be pretty specific to just the wanting component and not the liking. And this is really different from what I think the popular imagination for dopamine tends to be, which is a reward molecule, a happiness molecule.

Nicholas Weiler: Let's actually go back for a second. So this all goes back to some of the earliest studies with dopamine. This is this classic study with a rat and a lever. We can link to an amazing video of this in the show notes, but could you describe that classic study and what the interpretation of that was at the time and how that's shifting now?

Neir Eshel: So one of the reasons that I've been obsessed with dopamine for a long time is because I've watched a bunch of these YouTube videos of these classic experiments from the 1950s and on, in which the experimenter would stick an electrode in the brain of an animal like a rat, and then allow the animal to press a lever to run a little pulse of electricity through that electrode and stimulate that part of the brain. And you can see these videos that the rat would just keep on pressing, even if it has to undergo all sorts of negative consequences, all sorts of punishments, for example, it gets a shock on its feet, and yet it will still keep pressing for that stimulation of the brain, despite the fact that it knows that it's going to also get shocked for it, and it will do that even at the expense maybe of eating or of mating or other things that it definitely wants to do. And what the scientists found is that this brain stimulation reward, which is what it was called, is fully dependent on and driven by dopamine release.

Nicholas Weiler: And so that naturally led people to think about pleasure and pain. This was very much in the milieu at the time. There was behaviorism like in psychology that was saying that all behavior is based on balancing pleasure and pain and seeking pleasure and avoiding pain and so on. So if you can stimulate this area and the rat will do anything for it, even overcoming negative stimuli, this must be the pleasure center of the brain. And so that was the idea for a long time. But as you said, we've started to realize that it's not quite so simple as that.

 I'd love to talk a little bit about your recent study now, because I think it's a really nice example of this difference between what we like, what's pleasurable and what we want, what we're motivated to go out and get. And this is subtle and a little bit difficult, but I think it potentially has profound implications. So let's try to get into this. How did you go about separating these components of liking and wanting in your study?

Neir Eshel: The way that we did this was to ask the animals to work various amounts to gain access to a reward that they wanted. So in this case, the first thing that we tried was a little squirt of sugar water. And what we did is we trained them that if they poke their noses in a particular part of a box enough times, they would get a little squirt of sugar water. So at first, they just had to poke their noses once or a couple times in the right place, and then we would give them the sugar water, but eventually we trained them so that they would poke up to almost 50 times for a single squirt.

Nicholas Weiler: That's a lot of work for a mouse, right?

Neir Eshel: It's a lot of work for a mouse. It takes time. It's kind of annoying as you might think. All you want is some sucrose and you need to poke dozens of times in this particular small little hole in order to gain access to it.

Nicholas Weiler: You've basically given it a boring desk job.

Neir Eshel: We gave it pretty much a boring desk job in which it just had to repeat the same action over and over again, and eventually it would get the thing that it wanted to get. And so what we asked is how much of that reward would it get at various different costs? So if we made it super easy, you just had to poke one time to get access to that sugar water. How many of those squirts of sugar water did it actually want until it just kind of got sick of it? It reached its level of desire and it stopped working for it. And then how did that compare to another scenario in which for each sugar water it needed to work harder? And so we just modulated the price of the sugar water, and by price I mean how many times the animal had to poke its nose. And we observed how changes in the price modified the number of rewards that the animal would ultimately consume. And the reason that we did this modulation is exactly as you mentioned, so we could dissociate the wanting versus liking.

 So if you think about if you were given unlimited cupcakes and they would just kind of hand it to you, maybe you would have one or two, but I doubt that you would have 20 because that just would kind of make you sick. There's a limit to how many cupcakes you actually want at any given unit of time.

Nicholas Weiler: And so then you're trying to find how much it values the reward, the cupcake?

Neir Eshel: We were trying to find how sensitive the mouse is to increases in price. So as the price goes up, how rapidly does the consumption go down? So in this case, if you really want that cupcake, you're willing to spend a hundred dollars for one maybe. At some point the price is too high and you eventually won't pay it, and you will consume fewer rewards. But there is this sweet spot in which you want something enough that you're willing to continue to increase the cost. In this case, the mice are willing to continually increase the number of times they poke their noses in this small little place to gain access to a single squirt of sugar water.

Nicholas Weiler: Okay. And so then where does dopamine come into all this? So you can measure how the animal is doing sort of a cost benefit in its head, how much it's going to work for this reward, and as the work goes up, its motivation to do it goes down. So where does dopamine come into the story?

Neir Eshel: So the reason that we're using mice and not people in cupcakes here is that we have all these amazing tools to study the release of dopamine as the animals are actually performing this task. And not only can we record variations of dopamine release, we can even manipulate the dopamine levels in real time. We can stimulate or inhibit the release of dopamine and see how that affects the animal's behavior on this task. And so what we did is we took advantage of the fact that this task varies how much the animal is working for reward, how many times they have to poke their noses for it, so we can directly map that cost element onto the dopamine release that we're recording at the same time.

 One of the amazing findings was that the dopamine release was heavily dependent on cost. So if the animal got the same exact reward, the same little bit of sugar water, the dopamine release to the same exact reward varied as a function of how much the mouse had to work for it. If the mouse worked really hard for the same reward, more dopamine was released than if the mouse worked less hard for the exact same reward. And to us, that was really exciting because it gave us the sense that dopamine might have something to do with what's called a sunk cost or how much you've already paid for a given reward. Seems like the mice are valuing the rewards more, which is reflected in the increased dopamine signal, if they worked harder for it, even though the reward itself is identical.

Nicholas Weiler: Interesting. Okay, so you're showing that the dopamine doesn't seem to care how much the animal enjoys the reward, whatever it is. It just seems to care about whether the animal is willing to put in the work and potentially whether it has already put in enough work that it wants to just finish and get the thing. That's really fascinating because I think that this distinction between liking and wanting is really at the core of our confusion about why we do what we do. This is something that I brought up earlier.

 So I'd love to take a step back now. Now that we've seen this, you can show in the brain that there's a difference between what an animal enjoys and what an animal is willing to do. One of the things I find so interesting is that in recent years, there's also been this convergence between a whole other area of studying dopamine, which is in disorders like Parkinson's disease, well, specifically in Parkinson's disease, it's the dopamine neurons that are degenerating and leading to an inability to initiate behavior and inability to move. That seems so different from the way we had thought about dopamine in these classic rat studies where the animal's pressing the lever, and it seems like it's some kind of pleasure or reward, but what does pleasure and reward have to do with Parkinson's disease?

 But this idea that dopamine is somehow related to your motivation to do something and the connection that you already made to drug addiction, that there's a high motivation state that overrides even very severe costs, it starts to make sense of the other roles of dopamine in the brain. I'd love to hear your hypothesis about dopamine regulation in the brain and how it's related potentially to many different psychiatric and neurological conditions, that there's some places where dopamine may be too low, some places where it may be too high. What is your thinking or the thinking in the field on that right now?

Neir Eshel: Dopamine is a extremely impressive molecule in my opinion, and so I don't want to claim that there's just one thing that explains all of dopamine's function, but I do think as you mentioned, that there begin to be certain patterns that emerge when you start looking at the functions that have been ascribed to dopamine in various regions and in various clinical contexts.

 Parkinson's disease is a great example of this, which is a disease of dopamine neuron degeneration. The dopamine neuron die and certain neurons die first, and those are the neurons that are most associated with the initiation of movement. And so you have patients that are at a door and they simply can't walk across the threshold, that initiation step, that just doesn't happen. The same person if a ball is thrown to them, can rapidly move up their heads and catch it or they can dance. So there's all sorts of other things that if driven by an external stimulus, they can still do, but it's that kind of self-driven initiation of behavior that is particularly dysfunctional in that context. And if you replenish dopamine for these patients with Parkinson's disease, they can initiate movements. It's really incredible.

Nicholas Weiler: So this may be a total oversimplification, but I mean, do you see that as the flip side of dopamine in addiction where people are driven to do things even when there's a really high cost?

Neir Eshel: Absolutely. I think there's a definite connection there. Now, again, there are different populations of dopamine neurons. There's a diverse set of dopamine neurons that are sending projections to various different parts of the brain and probably having different functions. So again, I don't want to claim that it's all one thing, but there is a connection between the kind of hyper elevated dopamine that you might see in response to a drug of abuse and the depleted dopamine that you see in a condition like Parkinson's disease. A lot of that connection I think does have to do with action and the value of action.

 And if you have too much or the dopamine is released to a too high extent because that's what drugs of abuse tend to do, they eventually can lead to this action at the expense of, or regardless of really harsh, negative consequences. And on the other hand, if you don't have enough dopamine because the dopamine neurons are dying in Parkinson's disease, now all of a sudden you're unable to initiate those actions at all. So you can see this kind of two ends of a very wide and important spectrum of the control of our behavior.

Nicholas Weiler: That's so fascinating. I think starting to see dopamine in a slightly more nuanced and complex light is helping the field get closer to really understanding both addiction and Parkinson's and a whole host of other disorders where this may be a factor.

Neir Eshel: Absolutely. So other disorders that I think about a lot and I see in clinic include depression. Anhedonia in depression is this classic core symptom, which is usually defined as an inability to experience pleasure. I think that's too narrow a definition for anhedonia. I like to think of it as any deficits in reward seeking. And as I mentioned before, I like to think of reward seeking as having at least two variables, the wanting and the liking. And so when I see patients in clinic with depression, sometimes people will tell me they would like the reward just fine. So they would like playing that video game. They would like hanging out with that friend. They would like eating that food if it were brought to them, if they didn't have to leave the bed the home in order to do it. So the reward feels okay, but it doesn't feel worth the effort.

 And then there are other people who come in saying that, "Yeah, even if you just gave that to me for free, I wouldn't really enjoy it. It just doesn't feel good anymore." I think of those as both potentially described by anhedonia, and they can both be very prevalent in depression, but to me, they feel different. In one case, it's a deficit in wanting, in another case, it's a deficit in liking, and my hypothesis is that the people who are telling me that they can still experience some joy or pleasure with something that they used to enjoy, but they just don't feel like it's worth the effort. It's possible that those people would be particularly helped by dopamine targeting drugs, whereas there may be other types of medications or treatments that are more effective for people whose deficit is more in the liking component.

Nicholas Weiler: That makes so much sense. I just wanted to ask one more thing to just take yet another step back. We started by talking about how humans don't always make the greatest decisions, or we don't always know what is good for us. We've talked about sunk cost and we've talked about really extreme cases like drug seeking in addiction and the inability to exert effort to get a reward or to do regular behavior in Parkinson's or depression. In a more everyday sense, does this changing perspective on how the brain is perceiving motivation and this wanting and how that's set in the brain, does that help us shape our own behavior, or at least be empathetic about where our behavior is coming from?

Neir Eshel: I think it does. It might or has the potential to. I see patients in clinic all the time whose behavior is different from their values. They know that, and they tell me that, and yet they seem driven to do it for one reason or another. There are so many examples of this. And for a clinician, I think it can be a little disheartening because there are people who come in and they want help, but you give them suggestions or you try a treatment and it doesn't necessarily change their behavior, even if they want to change their behavior and I want to change their behavior. Everyone's on the same page and yet this doesn't change, or it takes a long time to change.

 I think for me, knowing a little bit more about the dopamine system and how there's a difference between wanting and liking and how types of behavior, for example, drug-seeking behavior sometimes can become hardwired over time because of the ways that dopamine works in our brains. To me, that makes me more patient. It makes me more empathetic or understanding of the struggles that people go through on their daily lives, and it makes me less likely to judge someone just because their behavior isn't consistent with their own values or their own goals. Because I know that it's complicated in there, in the brain, and that sometimes things that take years to develop might also take years to change.

Nicholas Weiler: Well, I would love to talk more about how dopamine changes behavior and what we can do to change problem behaviors and all of that. That would be a great additional conversation, but I think we're going to have to save that for next time. Thank you so much, Neir, for joining us on the show.

Neir Eshel: Absolutely. Thanks for having me.

Nicholas Weiler: Thanks again to our guest, Neir Eshel. We'll include links for you to learn more about his work in the show notes.

 If you're enjoying the show, please subscribe and share with your friends. It helps us grow as a show and bring more listeners to the frontiers of Neuroscience. We'd also love to hear from you. Leave us comments or give us a shout-out on social media. We are at Stanford Brain.

 From Our Neurons to Yours is produced by Michael Osborne at 14th Street Studios with production assistance from Morgan Honaker. Our logo is by Aimiee Garza. I'm Nicholas Weiler at Stanford's Wu Tsai Neurosciences Institute. See you next time.

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