Selects: How Dopamine Works  ## Highlights - **Dopamine Is A Signaling Molecule Not Just Pleasure** - Dopamine is not just a "pleasure chemical"; it primarily acts as a signaling neurotransmitter that helps neurons communicate and form behavioral connections. - Josh and Chuck emphasize dopamine's broad roles beyond pleasure, including motivation, focus, and learning, reshaping common misconceptions. Transcript: Josh And it's a wonderful segue, too, because it just so happens that today the topic of this episode is dopamine. And there's probably no more misunderstood neurochemical, certainly neurochemical, maybe substance in your body at all than dopamine. We used to think we had a really great handle on dopamine and what it does and how it works. And it turns out that we are at every turn, a new study comes along that says, nope, we're wrong. Yeah, we're wrong about that. Well, what about, yep, wrong about that. Basically, everything we know in popular culture. And I mean, if you've even gone to like Cleveland Clinic website or WebMD website or Harvard Health has some articles, you'll see this old, antiquated, outdated view of what dopamine Is being kind of paraded around. The idea that it's a pleasure-inducing chemical, that if something gives you pleasure, you're responding to a hit of dopamine. And that is just absolutely not true. Chuck Yeah, and this may be the most oft-covered stuff-you thing that hasn't gotten its own title yet. Yeah. Josh Man, dopamine is the reigning champ right now. Yeah. Chuck We talk about this stuff all the time, it seems like. Josh Yeah, we do because it comes up a lot. And the reason why is because it turns out it has a lot to do with more than just pleasure. Like everybody, yes, it is associated with pleasure, just not the way we've thought for very long. And it does a lot of other stuff too. Essentially, what it does is it signals things. It says, hey, you behave or you act up. You stop behaving. Something like that. I'm not quite sure exactly what it says. I don't speak dopamine. But it's a neurotransmitter. So it's a chemical messenger in the brain at base. ([Time 0:03:21](https://share.snipd.com/snip/5d69268a-60f9-4502-8dbd-e5d689102b92)) - **How The Brain Makes Dopamine From Tyrosine** - Dopamine is synthesized in the brain from tyrosine via tyrosine hydroxylase because dopamine itself cannot cross the blood-brain barrier. - Josh notes humans produce about three times more dopamine than other primates, linking it to our learning and success. Transcript: Josh Sure. So the whole thing starts. It turns out that dopamine is used throughout the body, but for the most part, it's used in the brain. The problem is, is if you like had a big handful of dopamine and you just shoved it in your mouth, it couldn't make it into your brain for use. It can't cross the blood-brain barrier, in other words. Fortunately, the thing that makes dopamine up, its essential ingredient, tyrosine, an amino acid, can cross the blood-brain barrier, and when it gets there, it gets a big fat hug from Something called tyrosine hydroxylase. And that converts it into dopamine. And all of a sudden, your brain's like, yes, let's go. That's right. Chuck And we've known about it a long time. It's been around a long time. It is not exclusive to human beings. Josh No, that's a big one. Chuck Yeah, it's in all kinds of animals. But we are really kind of great at making it. And I was about to say hooked on it, but that implies the whole addiction thing. And I don't want to go down that road. But humans love this stuff. And we produce about three times as much as other primates do. Josh Yes. And, in fact, Emily Deans wrote an article in 2011, I think, on Psychology Today. ([Time 0:06:08](https://share.snipd.com/snip/055fff17-d0d3-4154-9fa7-a8a594bd3916)) - **Four Dopamine Pathways Drive Different Functions** - Different dopamine pathways produce distinct effects: nigrostriatal for motor control, mesocortical for executive function, tuberoinfundibular for milk suppression, and mesolimbic for reward and addiction. - Chuck and Josh link pathway-specific dysfunctions to conditions like Parkinson's and addiction. Transcript: Josh Yes. So there's D1 to D5, I think, types of receptors, dopamine receptors, and four pathways that they follow. And like you said, depending on what receptor is being activated and what pathway is being followed, all sorts of different stuff can happen. Dopamine is associated with motor control, learning, memory, malfunctions in it can result in psychosis. They use dopamine as a vasostimulant to treat heart conditions. It has just a cluster of different effects on the body depending on where it's being processed, like what pathway it's being processed. Right? And I think I said there's four of them total. Chuck Did you want to talk about those? Josh I feel like we should. Chuck Okay. The first one is the nigrostriatal tract. Nice. You mentioned motor control first, and that's the tract that has to do with motor control. Yeah. Josh So if those aren't working correctly, the dopamine neurons or the dopaminergic pathway in the nigrostriatal tract, that can result in Parkinson's. It's very famously associated with dopamine for anybody who has read or saw the movie. Chuck Yeah. Josh Which we'll probably talk about a little bit more later. That movie? Chuck Yeah. Josh Okay. I got a great, great bit up my sleeve. Okay. Chuck The second pathway is the mesocortical pathway. That has a lot to do with executive functioning. Yeah. Stuff, how your brain plans things, how it files away stuff, and how it, you know, how it organizes your overall sort of priorities. Josh Yes. And now it's time to talk about the most random dopaminergic pathway of all, the tubero and fundibular pathway. Tubero and fundibular. Yeah. I think you had it right the first time. Okay. We'll edit out the second one then. All right. We'll put in a slide whistle over it. So that connects the hypothalamus and the pituitary gland. And from what I can tell, I was like, well, what else does it do? The sole role of this pathway is to block the production of milk. Yes, to prevent the production of milk in the female breast of mammals. That's what it does. That's that pathway's role. And if you block that pathway, the milk production begins. Isn't that interesting? Chuck Yeah. We talked about that in the two-parter, the old breastfeeding two-parter. Josh Oh, we did? Oh, yeah. Oh, I don't remember that. Chuck Yeah, yeah. Josh Wow, you've got a great memory. That's where it all begins. Chuck No, I have a terrible memory. I know you're making fun of me. There's also the mesolimbic ([Time 0:09:52](https://share.snipd.com/snip/0b52d022-a39e-466b-af24-46bcb7529607)) - **Dopamine Release Is Precise And Millisecond Fast** - Dopamine release is fast and targeted, not slow and diffuse; precise millisecond squirts hit specific neurons rather than a brain-wide wash. - Josh cites a 2018 Harvard paper overturning the old "volume transmission" idea about dopamine. Transcript: Josh Right. Here's a great example of just how wrong we got dopamine. It turns out the process that dopamine is excreted and crosses into the synapse and creates like an electrical transmission in the brain is the exact opposite of volume transmission. It could not be more opposite than the idea that it just floods slowly across the brain and whatever it runs into, it runs into. We found that in milliseconds, a precise squirt of dopamine hits exactly the right neuron in exactly the right places, right on the money. That's how dopamine is excreted. The exact opposite of volume transmission. Yeah. Chuck And we learned that not too long ago, 2018, medical researchers at Harvard released this paper and said, hey, guess what, everyone? It's the opposite of everything you've been saying. And everyone went, oh, okay. Sorry about that. Sure. Josh Might be. So after the dopamine is excreted and it does its job, it actually breaks down remarkably quickly. ([Time 0:14:13](https://share.snipd.com/snip/29813a23-53fd-4a59-b4b2-6591804cca1f)) - **Dopamine Drives Wanting Not Liking** - Classic rat experiments misinterpreted dopamine's role: dopamine depletion reduced motivation to seek rewards, not the capacity to feel pleasure. - Josh and Chuck explain later work showed lack of dopamine causes reduced wanting, not necessarily reduced liking. Transcript: Josh So check this whole, I should say, misunderstanding of dopamine as the ultimate pleasure chemical. If you take a drag off a cigarette, if you snort a line of Coke, if the person you love, like, touches your hand, if you get, like, an A from the teacher, like, you're going to get a hit of dopamine And that's what your reward is. It's pretty old. It's an old idea. At least it dates back to the middle of the 20th century, which is we're getting further and further away from, which makes me gulp. But that idea being discredited is pretty old too Like, it didn't last very long. The problem is its legacy stuck around for a really long time. It's still around today. Chuck Yeah, for sure. There was a researcher, speaking of old, named James Olds in the 50s and 60s who did some experiments with rats and said, hey, every time I give these rats a little electrical stimulation In just the right place, right there behind the ear, they're going to keep pulling that lever down or whatever act I'm making them do. They'll just do that over and over and over and over and over as long as I keep stimulating that area. Josh And what they said was, okay, there's something going on with dopamine in this, I guess, pleasurable act that the rat is doing to itself. And that got followed up in the 70s by a guy named Roy Wise who depleted dopamine receptors in rats and found that they would not seek out food and they wouldn't seek out methamphetamines That were just there on the offer. Those rats could have as much meth as they wanted. And they were like, nah, I don't want any. And crucially, critically, Roy Wise and his colleagues misinterpreted that as a lack of experience of pleasure, not a lack of motivation. And it wasn't until the 80s that some other people came along and were like, no, we've been getting this wrong all this time. Chuck Yeah, in the 80s, they used sugar instead of methamphetamine, I guess. And once again, very kind of cruelly, they cut off, they didn't allow them any dopamine. They killed them off with drugs. But this time they gave them the sugar and they said they're liking the sugar. You can tell by the look on that little guy's face that he enjoys it. But, and this is the key, it's not coming back and saying, give me more sugar, give me more sugar. Josh Right. Or give me more meth. Sure. So this whole thing, this changed our understanding, at least in the, like, academia among people who study this kind of thing. We realized we were misinterpreting what we were seeing and that a lack of dopamine didn't lead to a lack of pleasure called anhedonia or anhedonia. It was a lack of motivation to seek out that pleasure. That's the effect of not having enough dopamine that we found from Sure. Those rat tests. So like this whole new framework of understanding it kind of came along. ([Time 0:19:48](https://share.snipd.com/snip/5a07e368-1149-4951-af0b-50b2e40313d3)) - **Dopamine Functions As A Prediction Error Signal** - One theory frames dopamine as a prediction error signal measuring difference between expected and received reward, strengthening future behavior. - Josh explains larger positive surprises produce bigger dopamine responses and stronger learned connections. Transcript: Chuck There's one theory called a, that it's prediction error. So you get, you get more bang for your buck, basically. You expected to like that peanut butter pie, but this was the best peanut butter pie you've ever had. Maybe the best dessert you've ever had in your life. And you're like, wow, that your brain says that was way, way better than I thought it was going to be. So it reinforces it. Right. Josh And to put it in kind of computational terms, dopamine is a prediction error. Somehow that chemical measures the difference between what you expected and the amazing reward you got. And the greater the difference, the more pronounced a connection that dopamine is going to make between going and getting peanut butter pie and eating peanut butter pie. So you'll have more motivation to do it next time. Chuck Yeah. The other way of thinking about it is the dopamine itself is the motivational signal. ([Time 0:25:10](https://share.snipd.com/snip/65e30131-5c61-4bf5-927a-c0ea5a69c7ca)) - **Awakenings Shows Dopamine Restores Motivation To Move** - Oliver Sacks' Awakenings cases show dopamine can transiently restore movement in frozen encephalitic patients, demonstrating its motivational power. - Josh recounts patients catching oranges or rushing to save a drowning person after dopamine stimulation. Transcript: Josh Awakenings anecdote comes in. Let's hear it. So you were talking about how, you know, the peanut butter pie motivating you to get out of bed and actually go. That definitely jibes with research, particularly something reported by Oliver Sacks in the book and then later the movie Awakenings. There was an epidemic of something called encephalitic lethargia, which is what happened to Robert De Niro's character. Remember, as a boy, he caught this thing and he just kind of froze in place. It's where you develop Parkinson's symptoms so much that you just don't, you can't move. You cannot move. You don't have the required dopamine to actually move. So you're just sitting there frozen in place like a statue. But anybody who saw this movie remembers being amazed by this scene. If a certain patient is stimulated, their dopamine is stimulated just enough, they can actually overcome that being frozen in place. And so there's a famous scene where Oliver Sacks tossed one of the patients some oranges and she caught them. Like she was a frozen statue and all of a sudden she's catching oranges and then juggles with them. Or there's another patient that was on the beach, I believe in their wheelchair, saw someone drowning and was motivated to get up and go save the person and then come back and go back to This frozen statue kind of stasis. ([Time 0:26:20](https://share.snipd.com/snip/5ace5a7a-82b6-4e97-8d1c-4196cad15db2)) - **Addiction Strengthens Connections And Downregulates Receptors** - Addiction involves strong learned connections: intense rewards produce big dopamine floods that tightly link a behavior to reward, and repeated floods cause receptor downregulation. - Josh explains downregulated receptors require more drug to achieve prior effects, contributing to escalation. Transcript: Chuck We talked about it plenty of times, certainly in our addiction podcast episodes. But it does play a pretty big role in drug abuse and addiction. It does reinforce the, you know, the idea that you want to keep using those drugs because it's making you feel good. And when we're talking about, you know, you're talking about the woman juggling oranges in that movie and how remarkable that is. Right. If they've given you Parkinson's drugs and they just flood your brain with dopamine, they found that 10 percent of the people that have had that treatment turn into gambling addicts. And I would imagine there are people who already gambled. I don't think it like drove them to start gambling. But that just goes to show you the power of like what a flood of dopamine will do to your brain. And it's pretty clunky way to deal with it, I think. Josh Yeah, I think that's what you were referring to earlier when you were saying like that understanding of volume transmission theory of dopamine release. That's what the drugs are based on, that understanding and that misunderstanding. And like, yeah, that's what happens. It's like, yes, if it does crawl across the brain and runs into whatever neurons that it can trigger, it's going to have all sorts of other knock-on effects. Yeah, totally. So, I guess our current understanding of how dopamine relates to addiction is that it connects drugs with pleasure. And as I was saying before, the more intense the experience, especially the reward, you can have a negative experience. And I think they're starting to figure out dopamine has something to do with that, too. But as far as we know, the more intense the reward, the greater the flood of dopamine. And so the greater, the stronger the connection you make between, you know, pressing a lever and a scientist giving you a bunch of meth. Yeah, absolutely. Chuck But that is, to be clear, just part of the recipe of what leads to addiction. I don't – maybe there are people out there saying that, but I don't know if anyone really is saying, like, it's all because of dopamine. No. It is part of the recipe in addition, obviously, to your genetics. Just the fact that drugs are out there and available and there are environmental pressures and influences. All kinds of reasons that people start to take drugs or continue to take drugs. And as far as the continuation, dopamine is definitely a part of it. Josh Right. And so one of the ways that you learn to take drugs is not just from the fact that your brain is flooded with dopamine, which allows you to make that connection very strongly, but the brain Actually changes in response to those increased floods of dopamine because it's not set up to release dopamine like that repeatedly over long periods of time. ([Time 0:29:58](https://share.snipd.com/snip/2b5a8fbc-6a16-48bb-a7ad-4694a5c26907)) - **Autoreceptor Count Affects Risk Taking For Gains** - Individual dopamine system differences correlate with risk-taking: fewer autoreceptors amplify dopamine's effect and link to greater risk-taking for potential gains. - Chuck cites studies where boosted dopamine increased risky choices when rewards were possible. Transcript: Josh And, in fact, they find that they have fewer what are called autoreceptors. Apparently, over time, we've evolved to create on dopamine neural cells a site called an autoreceptor that actually catches some of the dopamine. It helps regulate it. Like, it never makes it out. So it keeps the amount of dopamine down to a regulated level. So the fewer autoreceptors you have, if you're still pumping out dopamine, you get a much greater impact from that dopamine. And they have correlated that to risk-taking. People who have fewer dopaminergic autoreceptors take more risks, at least according to some studies. Yeah. Chuck And they've also done studies where they found that that risk should or needs to be tied to a reward, like a gain, basically. There was a study from the University of College in London in 2015 that said subjects whose dopamine levels was higher, it was boosted artificially with medication, would choose risky Options more often if it involved a potential gain. They didn't see that same thing going on if there was a potential loss involved. So there's definitely a tie to a gain or another way of saying that would be a reward. ([Time 0:36:01](https://share.snipd.com/snip/cd2c4615-55fb-4e62-bf2d-0dd5f80eda35)) - **ADHD Relates To Dopamine But Mechanisms Remain Unclear** - ADHD links to dopamine differences but causation is unclear; dopamine likely drives some ADHD symptoms like impulsivity and poor impulse control. - Josh cautions there's no single ADHD brain pattern yet and research is ongoing. Transcript: Josh Then also that impulse control is also a huge hallmark of ADHD symptoms. And so ADHD is very commonly associated with some sort of dopamine deficiency. And from what I've seen, there isn't a, like an across the board, we haven't discovered some across the board type of brain that's like, yep, if you have this brain, you have ADHD and vice Versa. And we're not even certain exactly what effect the dopamine is having. We're almost just kind of like seeing effects that are the behavior of people with ADHD and saying, hey, we know that dopamine does that. Or if you don't have dopamine, you're more likely to do this. So there's this correlation. It's just not – it's never been like completely shown yet. I think it probably will be at some time, but we don't really know how ADHD is linked to dopamine. But there's, we're almost certain that dopamine drives at least some of the ADHD symptoms. It's just because of that, people have made leaps in understanding. Like there's a longstanding myth about people with ADHD that they do these impulsive behaviors to get a hit of dopamine. Well, it's based on that old idea that dopamine is a pleasure-producing chemical or reward-producing chemical, where instead it might be that people do these behaviors that are impulsive Because they don't have the dopamine that can regulate their impulses. And so they have less impulse control. We're just still sorting it out, I guess. Chuck Yeah. All right. Should we take our final break here? Yeah. Josh All right. Chuck We'll take a break and we'll talk about, oh boy, it's going to be so much fun, social media right after this. ([Time 0:37:17](https://share.snipd.com/snip/69acf56f-dbbe-4a02-b7aa-a094889a3aec)) - **Limit Social Media By Breaking Random Reward Loops** - Reduce compulsive social media use by recognizing platforms exploit dopamine-driven random reward loops to keep you returning. - Josh and Chuck point to Chamath's admission that notifications and unpredictable rewards were engineered to create short-term dopamine feedback loops. Transcript: Chuck Everyone is pretty hip to the fact now that notifications and the dings and the likes and the loves and the hearts and all the things that come through various interacting with various Social media platforms. You just sounded so old, dude. Josh I know. Chuck That's great. In this case, I love being old. I don't want any of it. I'm with you. But in any case, all of that stuff combines to give you a hit of dopamine and it's specific and you're like, fine, that's great, whatever. But it's specifically structured and built that way and coded that way so that you will become addicted to that social media platform. And they have admitted as such in 2018 it was a big news item when they were, I don't know, it was like congressional testimony or something. Can't remember exactly, but there was a VP at Facebook who came out and was basically like, hey, this is something we did on purpose. And it was a core foundation was the really the quote that kind of stuck out with how people behave using our platform. Like it was a part of the core strategy to get people to come back again and again and again. Josh Yeah, and that strategy was based on this was Chamath Pali Hapidia, who was a VP of user development at Facebook. And they said that this was based on short-term dopamine-driven feedback loops. And, you know, this is all old news to us now. I mean, this was six years ago. Think about how much our understanding of what social media does to us. But in 2018, that was a groundbreaking admission. But it's true. And, I mean, that's essentially how social media works. Like you get the app and you start to realize that if that little badge number comes up and says, hey, you have like two notifications, you go into it, you're going to get some sort of reward Of some sort. You're going to, like you said, get a ding or a like or a heart or something like that. And that is a reward to you. And so based on the mesolimbic theory of dopamine, we get a dopamine hit and so we learn to come back. And apparently also randomness has a lot to do with it. Because as we start to be able to predict when we'll get a reward, that dopamine stops being a part of that whole experience. So if it can be done randomly, we don't know when we're going to get a reward. ([Time 0:42:40](https://share.snipd.com/snip/16eca745-1ea7-4939-a16a-4bdeabeef5e5)) - **Treat Dopamine Fasts As Behavioral Breaks Not Neurochemical Cleanses** - Don't conflate "dopamine fast" with literal neurotransmitter fasting; instead, take intentional breaks from compulsive behaviors and replace them with meaningful activities. - Josh and Chuck note Dr [Sipa] meant stepping back from habits, not starving your brain of chemicals. Transcript: Chuck Who came out and said, all right, there's this term that I'm going to float out there, and it's called a dopamine fast. And the idea when that was floated was people heard that and they said, oh, well, dopamine just means just it's just a catch all term, basically, for for any sort of addictive behavior Like reinforcement. And you can go on a dopamine fast and like, you know, put that social media app down for a couple of weeks. And when you come back, it's just like your brain's going to have a little rest from that thing. And you're going to feel amazing about how much you love it when you come back. And that's not at all what Dr. Cameron was talking about or meant. No, huh? Josh Dr. Sipa Sipa was basically saying like, like he really misused dopamine fast. And he even said to the New York Times, like, I didn't mean it like that. Don't take it like that. I don't mean it literally. Everybody said too late. We're going to take it literally. And so there was this movement, I think people still do it, of self-denial of everything from, like, people stopped interacting with other people. People stopped eating foods they found pleasurable. They stopped talking if they didn't need to. Anything that could conceivably give you a release of dopamine. And their premise was that if they did that, it would be like going and drying out on heroin or cocaine so that when you come back, that first experience again with heroin or cocaine is That much more amazing because you've kind of replenished your endocannabinoids and opioids and all that stuff. Dopamine does not work like that. If you stop flooding your brain with dopamine, it doesn't replenish. It doesn't need to replenish. That's not how it works. But that's what people were doing. They just completely misinterpreted it. And it was based on faulty science and Dr. Sipa essentially using the wrong term. Chuck Yeah, I think the idea that he was talking about was, hey, put that stuff down and go do other things that you find pleasure in. Right. Live in the world or go out in nature or, you know, kind of get a hold of your life again so you don't feel like you're, you know, tied to this social media app for your happiness. Josh Yeah. Our moms used to call it going to play outside for a while. Right. Or summer, I think, is another term it used to be called. Yeah. But instead, this guy called it a dopamine fast, and people really took a left turn with it. So he identified six compulsive behaviors or categories that he was saying, you could really do good for yourself by taking a dopamine fast or a break from emotional eating, excessive Internet usage and gaming, gambling and shopping, porn and masturbation, thrill and novelty seeking, which I took to mean taking a break from thrill kill murder sprees. Right. And recreational drugs. Yeah. But he also said, you know, anything that you feel like has got a hold on your life, if you just stop and step away from it, it will have less a hold of your life. So TV would definitely be in there probably for a lot of people. But if you step back and look at what this guy's talking about, it's the most basic thing that people have been doing for eons. And yet just by slapping dopamine fast on it, it became sticky and buzzy and brainstormy or javasormy and like super corporate. ([Time 0:45:35](https://share.snipd.com/snip/f264324a-9c59-4acd-88ac-cf3a4a57c3e0))