WEBVTT - Selects: How Dopamine Works 0:00:00.680 --> 0:00:05.840 Hey, everybody, Happy Saturday. Chuck here with a curated selects 0:00:05.840 --> 0:00:09.280 episode in which we bring out a classic from dusted 0:00:09.360 --> 0:00:11.320 off from the old dustbin so you can give it 0:00:11.320 --> 0:00:14.120 a listen. This one is called how Dopamine Works, and 0:00:14.160 --> 0:00:16.600 it's one of obviously one of our more sciencey episodes. 0:00:16.640 --> 0:00:19.720 And I managed to struggle to get through it, because 0:00:19.720 --> 0:00:21.599 you know, I'm not good at these. But it was 0:00:21.640 --> 0:00:27.880 a great episode, so I hope you like it. Welcome 0:00:28.040 --> 0:00:35.240 to Stuff you Should Know, a production of iHeartRadio. 0:00:37.040 --> 0:00:39.680 Hey, and welcome to the podcast. I'm Joshing. There's Chuck 0:00:39.680 --> 0:00:43.280 and Jerry's here too. The three amigos back together again 0:00:43.360 --> 0:00:47.280 after some massively triumphant live shows. 0:00:48.720 --> 0:00:52.680 Yeah, we did a little Northeast Spring swing. 0:00:53.159 --> 0:00:55.000 Yeah, and it was great. 0:00:55.120 --> 0:00:59.600 It was a good show. Which one the podcast topic 0:00:59.760 --> 0:01:02.080 that did that we did live? Oh, I know that 0:01:02.080 --> 0:01:02.840 we're doing all year. 0:01:02.920 --> 0:01:05.199 I got to it was pretty good. I love that 0:01:05.200 --> 0:01:05.800 that topic. 0:01:06.360 --> 0:01:08.039 That's what you call an on secuitter. 0:01:08.600 --> 0:01:10.440 But it does feel good to be back, doesn't it. 0:01:10.480 --> 0:01:13.120 Back in the studio, back doing what we're born to do. 0:01:15.400 --> 0:01:17.600 I kind of prefer on stage, but sure, this is 0:01:17.640 --> 0:01:18.440 great to do. 0:01:18.520 --> 0:01:21.039 You you like the thrill of the audience, the roar 0:01:21.040 --> 0:01:23.160 of the crowd, that bowl running at you. 0:01:23.840 --> 0:01:24.320 Yeah. 0:01:25.000 --> 0:01:29.000 Nice, I like it too, sometimes when I'm not totally 0:01:29.280 --> 0:01:32.480 terrified because I drank too much energy drinks. 0:01:32.880 --> 0:01:36.000 Well, I wonder if your dopamine receptors are functioning as 0:01:36.040 --> 0:01:36.440 they should. 0:01:36.640 --> 0:01:39.840 Yeah, that's a great question, Chuck. And that's a wonderful 0:01:39.840 --> 0:01:42.319 segue too, because it just so happens that today the 0:01:42.360 --> 0:01:46.800 topic of this episode is dopamine, and there's probably no 0:01:47.000 --> 0:01:53.360 more misunderstood neurochemical, certainly neurochemical maybe substance in your body 0:01:53.400 --> 0:01:56.680 at all than dopamine. We used to think we had 0:01:56.720 --> 0:01:59.240 a really great handle on dopamine and what it does 0:01:59.280 --> 0:02:01.920 and how it works, and it turns out that we are. 0:02:02.520 --> 0:02:05.600 At every turn a new study comes along that says, Nope, 0:02:05.600 --> 0:02:08.560 we're wrong. Yep, we're wrong about that. Well what about yep? 0:02:08.720 --> 0:02:13.040 Wrong about that? Basically everything we know in popular culture, 0:02:13.360 --> 0:02:15.440 and I mean, if you even gone to like Cleveland 0:02:15.480 --> 0:02:20.519 Clinic website or WebMD website or Harvard Health has some articles, 0:02:20.840 --> 0:02:26.480 you'll see this old, antiquated, outdated view of what dopamine 0:02:26.560 --> 0:02:28.720 is being kind of paraded around the idea that it's 0:02:28.760 --> 0:02:34.320 a pleasure inducing chemical. That if something gives you pleasure, 0:02:34.040 --> 0:02:36.440 you're responding to a hit of dopamine, and that is 0:02:36.560 --> 0:02:38.080 just absolutely not true. 0:02:38.840 --> 0:02:42.720 Yeah, and this may be the most oft covered stuff 0:02:42.760 --> 0:02:46.160 you should know, thing that hasn't gotten its own title yet. 0:02:46.400 --> 0:02:51.040 Yeah. Man, that dopamine is the reigning champ right now. 0:02:51.600 --> 0:02:53.919 Yeah, we talk about this stuff all the time, it seems. 0:02:53.639 --> 0:02:56.480 Like, yeah, we do, because it comes up a lot. 0:02:56.520 --> 0:02:58.120 And the reason why is because it turns out it 0:02:58.160 --> 0:03:01.280 has a lot to do with with more than just pleasure. 0:03:01.400 --> 0:03:05.280 Like everybody, Yes, it is associated with pleasure, just not 0:03:05.400 --> 0:03:07.600 the way we've thought for very long. And it does 0:03:07.639 --> 0:03:11.320 a lot of other stuff too. Essentially, what it does 0:03:11.680 --> 0:03:15.000 is it signals things. It says, hey, you you behave 0:03:15.160 --> 0:03:18.760 or you act up, you stop behaving, something like that. 0:03:18.840 --> 0:03:20.760 I'm not quite sure exactly what it says. I don't 0:03:20.760 --> 0:03:24.040 speak dopamine, but it's a neurotransmitter, so it's a chemical 0:03:24.040 --> 0:03:27.800 messenger in the brain at base. But it's associated with 0:03:28.040 --> 0:03:31.960 so many different things that of course dopamine comes up 0:03:32.000 --> 0:03:34.760 all the time in our podcast. 0:03:35.200 --> 0:03:38.920 It sure does. So it is, like you said, a neurotransmitter, 0:03:39.480 --> 0:03:41.720 one of more than a hundred of those bad boys 0:03:42.680 --> 0:03:46.040 functioning in our bodies, and it, like you said, it 0:03:46.120 --> 0:03:52.560 lets things communicate. It's a facilitator, but it gets all 0:03:52.600 --> 0:03:56.200 the press for its you know, like the feel good 0:03:56.240 --> 0:04:01.360 stuff that you mentioned, addiction behaviors, whether it's gambling or drugs, 0:04:02.240 --> 0:04:05.040 or the thrill of you know those people that walk 0:04:05.040 --> 0:04:12.200 around on ledges and stuff. Ledgewalkers, Yeah, ledgewalkers. But it 0:04:12.240 --> 0:04:14.760 does all kinds of things. That's just the where it 0:04:14.880 --> 0:04:19.480 makes the newspaper headlines. But we should probably talk a 0:04:19.560 --> 0:04:24.000 little bit about just the narrow transmitter cycle that it 0:04:24.080 --> 0:04:24.640 goes through. 0:04:25.120 --> 0:04:28.320 Sure, so the whole thing starts. It turns out that 0:04:28.400 --> 0:04:33.120 dopamine is used throughout the body, but for the most 0:04:33.120 --> 0:04:35.560 part it's used in the brain. The problem is is 0:04:35.680 --> 0:04:38.359 if you like had a big handful of dopamine and 0:04:38.360 --> 0:04:40.920 you just shoved it in your mouth, it couldn't make 0:04:40.960 --> 0:04:44.479 it into your brain for use. It can't cross the 0:04:44.520 --> 0:04:47.880 blood brain barrier. In other words, Fortunately, the thing that 0:04:48.040 --> 0:04:53.480 makes dopamine up, it's essential ingredient tyrosine and amino acid, 0:04:53.800 --> 0:04:56.880 can cross the blood brain barrier, and when it gets there, 0:04:57.160 --> 0:05:03.600 it gets a big fat from something called tyrosine hydroxylase, 0:05:04.200 --> 0:05:07.320 and that converts it into dopamine and all of a sudden, 0:05:07.360 --> 0:05:09.360 your brain's like, yes, let's go. 0:05:10.320 --> 0:05:13.520 That's right. And we've known about it a long time. 0:05:13.560 --> 0:05:16.880 It's been around a long time. It is not exclusive 0:05:16.920 --> 0:05:17.880 to human beings. 0:05:18.040 --> 0:05:18.680 No, that's a bit. 0:05:19.480 --> 0:05:22.600 Yeah, it's in all kinds of animals. But we are 0:05:22.680 --> 0:05:26.640 really kind of great at making it. And I was 0:05:26.680 --> 0:05:28.640 about to say hooked on it, but that implies the 0:05:28.680 --> 0:05:30.960 whole addiction thing, and I don't want to go down 0:05:31.000 --> 0:05:34.760 that road. But humans love the stuff, and we produce 0:05:34.800 --> 0:05:38.039 about three times as much as other primates do. 0:05:38.720 --> 0:05:43.200 Yes, And in fact, Emily Deans wrote an article in 0:05:43.240 --> 0:05:47.360 twenty eleven I think on psychology today. She's an evolutionary psychiatrist, 0:05:48.040 --> 0:05:51.080 and she said that dopamine is what made humans so successful. 0:05:51.839 --> 0:05:55.599 And from what I can tell, the latest research about 0:05:55.600 --> 0:05:58.520 dopamine is that it essentially is what allows us to 0:05:58.600 --> 0:06:02.360 learn about the world around us. We make connections that 0:06:02.520 --> 0:06:05.640 collectively form our mental map of the world, of how 0:06:05.640 --> 0:06:08.360 we're to behavior on other people, of how we do 0:06:08.440 --> 0:06:11.760 things like go get food, like that dopamine is somehow 0:06:11.800 --> 0:06:17.080 behind all of it, and that because we're so responsive 0:06:17.120 --> 0:06:20.520 to dopamine and we produce so much dopamine compared to 0:06:20.560 --> 0:06:25.839 other animals in the animal kingdom. That is, conceivably what 0:06:26.000 --> 0:06:29.680 has allowed us to become as successful as we are 0:06:30.360 --> 0:06:33.520 compared to other animals in that nuts like it could 0:06:33.560 --> 0:06:35.560 all just come down to dopamine essentially. 0:06:36.560 --> 0:06:41.680 Yeah, man, opposable thumbs maybe. 0:06:40.360 --> 0:06:42.560 Sure, But I mean, what are opposable thumbs if you 0:06:42.600 --> 0:06:46.640 can't have get the wear with all the to move it. 0:06:46.880 --> 0:06:48.880 True, but if you had the wherewithal to move it, 0:06:48.960 --> 0:06:49.960 you could grab something. 0:06:50.120 --> 0:06:53.680 Yes, you can use the heels of both hands just 0:06:53.720 --> 0:06:54.360 like a thumb. 0:06:54.800 --> 0:06:56.839 Are you under selling the opposable thumb? 0:06:57.080 --> 0:06:59.920 Yes, I'm sick of the imposable thumb always hogging the spot. 0:07:00.279 --> 0:07:01.560 It's dopamine's time. 0:07:02.680 --> 0:07:04.840 You can get those removed. You know, see how you do? 0:07:05.279 --> 0:07:08.240 I guess that sounds like a dare to me, Chuck. 0:07:08.440 --> 0:07:09.920 Say goodbye to your tennis game. 0:07:10.720 --> 0:07:12.480 I can play it just by holding the racket with 0:07:12.520 --> 0:07:13.760 the both heels in my hand. 0:07:14.520 --> 0:07:16.800 I guess we should have said pickleball. That'd be more current, right, 0:07:16.840 --> 0:07:19.600 I don't play pickleball. I haven't tried it yet. 0:07:20.040 --> 0:07:23.120 I want to, though, Okay, Well, there's plenty of places 0:07:23.160 --> 0:07:24.520 and people to play it with. 0:07:25.400 --> 0:07:27.680 Yet I have found no one or no place. 0:07:28.240 --> 0:07:31.239 Oh, I'm sure somebody will write in and offer to play. 0:07:31.040 --> 0:07:34.080 With you, of course, and then I go out there 0:07:34.120 --> 0:07:35.679 and I like blow my acl or something. 0:07:35.960 --> 0:07:37.800 Oh god, that was nice. 0:07:38.720 --> 0:07:40.840 So at the highest level, you know, we kind of 0:07:40.920 --> 0:07:46.040 talked about this a thousand times before, but dopamine functions 0:07:46.120 --> 0:07:51.080 as a neurotransmitter. It enables signals to pass through these gaps, 0:07:51.120 --> 0:07:55.560 these synapses and make connection from neuron to neuron. And 0:07:55.600 --> 0:07:58.840 that's just sort of the bird's eye view. But there 0:07:58.840 --> 0:08:00.600 are all kinds of things that dope I mean does, 0:08:00.640 --> 0:08:03.800 and depending what kinds of neurons it's talking to and 0:08:03.840 --> 0:08:08.160 it's introducing to one another, it's gonna have different effects 0:08:08.200 --> 0:08:09.000 on the human body. 0:08:09.880 --> 0:08:13.120 Yes, So there's D one to D five I think, 0:08:13.640 --> 0:08:20.000 types of receptors, dopamine receptors and four pathways that they follow, 0:08:20.880 --> 0:08:23.640 and like you said, depending on what receptor is being 0:08:23.680 --> 0:08:26.800 activated and what pathways being followed, all sorts of different 0:08:26.800 --> 0:08:32.640 stuff can happen. Dopaminees associated with motor control, learning, memory. 0:08:33.240 --> 0:08:37.960 Malfunctions in it can result in psychosis. They use dopamine 0:08:38.000 --> 0:08:40.880 as a vaso stimulant to treat heart conditions. That has 0:08:41.040 --> 0:08:44.360 just a cluster of different effects on the body depending 0:08:44.400 --> 0:08:49.319 on where it's being processed, like what pathway it's being processed, right, 0:08:49.360 --> 0:08:51.440 And I think I said there's four of them total. 0:08:52.559 --> 0:08:53.480 Did you want to talk about this? 0:08:53.640 --> 0:08:55.720 I feel like we should. Okay. 0:08:56.080 --> 0:09:00.160 The first one is the nigros striatal tract. Nice, you 0:09:00.160 --> 0:09:03.280 mentioned motor control first, and that's the tract that has 0:09:03.320 --> 0:09:04.280 to do with motor control. 0:09:04.800 --> 0:09:08.959 Yeah, so if those aren't working correctly. The one that 0:09:09.000 --> 0:09:14.800 the dopamine neurons are the dopaminergic pathway in the nigrostriadal 0:09:14.880 --> 0:09:18.920 tract that can result in Parkinson's. It's very famously associated 0:09:18.920 --> 0:09:22.600 with dopamine for anybody who has read Awakenings or saw 0:09:22.640 --> 0:09:26.240 the movie Yeah, which will probably talk about a little 0:09:26.240 --> 0:09:31.040 bit more later that movie. Yeah, Okay, I got a great, 0:09:31.120 --> 0:09:32.880 great bit up my sleeve. 0:09:33.320 --> 0:09:37.720 Okay. The second pathway is a Mezzo Corty call pathway 0:09:38.280 --> 0:09:42.240 that has a lot to do with executive functioning, prioritizing stuff, 0:09:42.280 --> 0:09:45.920 how your brain plans things, how it files away stuff, 0:09:46.240 --> 0:09:49.800 and how it you know, how it organizes your overall 0:09:51.120 --> 0:09:52.120 sort of priorities. 0:09:52.679 --> 0:09:55.320 Yes, and now it's time to talk about the most 0:09:55.440 --> 0:10:02.000 random dopaminergic pathway of all the two bear fundibular pathway 0:10:02.679 --> 0:10:04.160 two boro in fundibular. 0:10:05.080 --> 0:10:07.240 Yeah, I think get it right the first time. 0:10:07.320 --> 0:10:11.199 Okay, we'll edit out the second one. Then we'll put 0:10:11.240 --> 0:10:14.280 in a slide whistle over it, so that connects us 0:10:14.320 --> 0:10:17.960 the hypothalamus and the petuitary gland. And it's from what 0:10:18.040 --> 0:10:19.520 I can tell, I was like, well, what else does 0:10:19.559 --> 0:10:22.920 it do? It's sole The sole role of this pathway 0:10:23.440 --> 0:10:27.360 is to block the production of milk or yes, to 0:10:27.600 --> 0:10:32.319 prevent the production of milk in the female breast of mammals. 0:10:32.559 --> 0:10:35.240 That's what it does. That's that that's that pathway's role. 0:10:35.760 --> 0:10:39.000 And if you block that pathway, the milk production begins. 0:10:39.040 --> 0:10:40.120 Isn't that interesting? 0:10:40.920 --> 0:10:43.920 Yeah? We talked about that in the two parter, the 0:10:43.960 --> 0:10:45.120 old Breastfeeding two parter. 0:10:45.280 --> 0:10:47.960 Oh yeah, oh I don't remember that. 0:10:48.800 --> 0:10:53.240 Yeah yeah, wow where No, I have a terrible memory. 0:10:53.320 --> 0:10:54.319 I know you're making fun of me. 0:10:54.960 --> 0:10:55.160 Uh. 0:10:55.200 --> 0:10:59.120 There's there's also the mesolimbic pathway. We've talked a lot 0:10:59.160 --> 0:11:04.559 about the Olympics in many episodes, but reward and emotion 0:11:04.800 --> 0:11:07.679 and this is the one where this is the one 0:11:07.679 --> 0:11:10.400 that gets all the pressed because this is the one 0:11:10.400 --> 0:11:13.480 that has to deal with addiction pleasure, and we're going 0:11:13.559 --> 0:11:17.200 to talk a lot about reward and how reward factors 0:11:17.200 --> 0:11:18.480 into how dopamine works. 0:11:18.600 --> 0:11:21.640 Right, This is the reason why some people get the 0:11:22.320 --> 0:11:28.239 chemical drawing of the molecular drawing of dopamine like tattooed 0:11:28.280 --> 0:11:32.720 on their wrists, because they're such so hedonic and into pleasure. 0:11:33.280 --> 0:11:36.000 That's why you might see somebody with that because of 0:11:36.040 --> 0:11:36.800 that pathway. 0:11:37.360 --> 0:11:38.040 I never heard of that. 0:11:38.440 --> 0:11:42.360 Yeah, it's a thing. Unfortunately it turns out to be 0:11:42.480 --> 0:11:45.679 a misinterpretation, but it is a thing that people do sometimes. 0:11:46.080 --> 0:11:51.040 Sure. So you know, we talked about misunderstandings about dopamine, 0:11:51.640 --> 0:11:55.079 and up until not too long ago, we didn't know 0:11:55.200 --> 0:11:59.480 a lot about exactly how dopamine worked in the body. 0:11:59.559 --> 0:12:02.880 And there was a misguided thought that there was something 0:12:02.920 --> 0:12:08.200 called volume transmission at work, which was you just sort of, well, 0:12:08.240 --> 0:12:11.400 you don't flood we'll talk about, you know, artificially flooding dopamine, 0:12:11.400 --> 0:12:15.680 which is also a problem that resulted from this misnomer. 0:12:15.720 --> 0:12:19.400 But dopamine just went very slowly, it was not very 0:12:19.480 --> 0:12:22.319 specific at all, just kind of washed over the brain 0:12:22.840 --> 0:12:26.240 and if it made some connections with various neurons, then 0:12:26.280 --> 0:12:29.200 that was kind of the dumb luck of dopamine, because 0:12:29.240 --> 0:12:30.440 dopamine is just dopey. 0:12:30.720 --> 0:12:33.480 Right. Here's a great example of just how wrong we 0:12:33.559 --> 0:12:38.040 got dopamine. It turns out the process that dopamine is 0:12:38.080 --> 0:12:41.960 excreted and crosses into the synapse and creates like an 0:12:42.000 --> 0:12:45.880 electrical electrical transmission in the brain is the exact opposite, 0:12:46.000 --> 0:12:47.760 totally volume transmission. 0:12:47.880 --> 0:12:48.120 Yeah. 0:12:48.200 --> 0:12:50.960 It could not be more opposite then the idea that 0:12:51.120 --> 0:12:53.800 just floods slowly across the brain and whatever it runs 0:12:53.800 --> 0:12:58.640 into it runs into. We found that in milliseconds, a 0:12:59.200 --> 0:13:03.880 precise squirt of dopamine hits exactly the right neuron in 0:13:03.960 --> 0:13:07.120 exactly the right place. It's right on the money. That's 0:13:07.200 --> 0:13:11.120 how dopamine is excreted, the exact opposite of volume transmission. 0:13:11.880 --> 0:13:14.840 Yeah, and we learned that not too long ago twenty eighteen, 0:13:15.679 --> 0:13:20.719 medical researchers at HAVID released this paper and said, hey, 0:13:20.720 --> 0:13:24.160 guess what, everyone is the opposite of everything you've been saying, 0:13:24.160 --> 0:13:28.360 and everyone want oh okay, sorry about that. Sure might be. 0:13:29.000 --> 0:13:33.920 So, after the dopamine is excreted and it does its job, 0:13:33.960 --> 0:13:38.280 it actually breaks down remarkably quickly. It turns into something 0:13:38.960 --> 0:13:42.880 it's metabolized and it is something called homovanillic acid, right, 0:13:43.760 --> 0:13:45.959 And from what I can tell, I don't know what 0:13:46.040 --> 0:13:50.280 the homo does to the vanillic acid, but vanillic acid 0:13:50.720 --> 0:13:53.600 is the flavor of vanilla. So from what I can tell, 0:13:53.640 --> 0:13:58.160 if you tasted the homovanillic acid, which is like the 0:13:58.200 --> 0:14:01.920 metabolite found in cirro spinal fluid that we test to 0:14:01.960 --> 0:14:05.000 see how much dopamine you have in your brain at 0:14:05.000 --> 0:14:09.640 any given time, it may taste like vanilla. Wow, isn't 0:14:09.679 --> 0:14:14.439 that interesting? It's gross. It is gross, and I don't know. Also, 0:14:14.440 --> 0:14:18.120 if we said that just twenty thousand neurons are capable 0:14:18.160 --> 0:14:22.840 of synthesizing dopamine, but that's a really small proportion of 0:14:22.880 --> 0:14:25.640 the total number of neurons we have to about one 0:14:25.680 --> 0:14:29.160 hundred billion, I think, yeah, absolutely, you want to take 0:14:29.200 --> 0:14:30.000 a break. 0:14:30.360 --> 0:14:33.240 Yeah, we'll break and we'll talk about, well what everyone 0:14:33.240 --> 0:14:35.760 wants to hear about, which is how dopamine and pleasure 0:14:36.440 --> 0:14:37.680 hold hands with one another. 0:15:01.560 --> 0:15:05.120 So check this whole under I should say, misunderstanding of 0:15:05.200 --> 0:15:08.680 dopamine as the ultimate pleasure chemical. If you take a 0:15:08.800 --> 0:15:11.160 drag off a cigarette, if you snort a line of coke, 0:15:11.280 --> 0:15:14.120 if if the person you love like touches your hand. 0:15:15.240 --> 0:15:19.520 If you get like an a from from the teacher, like, 0:15:19.560 --> 0:15:21.760 you're gonna get a hit at dopamine, and that's what 0:15:21.960 --> 0:15:26.080 that's what your reward is. That's it's pretty old. It's 0:15:26.120 --> 0:15:28.080 an old idea at least it dates back to the 0:15:28.160 --> 0:15:30.600 middle of the twentieth century, which is we're getting further 0:15:30.640 --> 0:15:35.440 and further away from which makes me gulp. But that 0:15:35.800 --> 0:15:39.120 idea being discredited is pretty old too, Like it didn't 0:15:39.200 --> 0:15:42.360 last very long. The problem is its legacy stuck around 0:15:42.440 --> 0:15:44.360 for a really long time. It's still around today. 0:15:45.280 --> 0:15:48.320 Yeah, for sure. There was a researcher speaking of old 0:15:48.480 --> 0:15:51.920 named James Olds in the fifties and sixties who did 0:15:51.920 --> 0:15:56.000 some experiments with rats and said, hey, every time I 0:15:56.120 --> 0:15:59.840 give these rats a little electrical stimulation and just the 0:16:00.080 --> 0:16:03.040 right place right there behind the ear, they're going to 0:16:03.160 --> 0:16:06.360 keep pulling that lever down or whatever act I'm making 0:16:06.360 --> 0:16:08.760 them do. That. They'll just do that over and over 0:16:08.800 --> 0:16:10.600 and over and over and over as long as I 0:16:10.680 --> 0:16:12.000 keep stimulating that area. 0:16:12.240 --> 0:16:16.600 Right. So what they said was, Okay, there's something going 0:16:16.600 --> 0:16:21.640 on with dopamine and this I guess pleasurable act that 0:16:21.800 --> 0:16:25.080 the rat is doing to itself, and that. 0:16:25.080 --> 0:16:27.120 Got followed up in Whoa, Whoa. 0:16:27.200 --> 0:16:29.200 That got followed up in the seventies by a guy 0:16:29.240 --> 0:16:35.000 named Roy Wise who depleted dopamine receptors in rats and 0:16:35.120 --> 0:16:37.760 found that they would not seek out food and they 0:16:37.800 --> 0:16:42.000 wouldn't seek out methamphetamines that were just there on the offer. 0:16:42.080 --> 0:16:44.120 Those rats could have as much meth as they wanted, 0:16:44.120 --> 0:16:46.600 and they were like, no, I don't want any. And 0:16:46.720 --> 0:16:51.880 crucially critically, roy Wise and his colleagues misinterpreted that as 0:16:51.920 --> 0:16:56.240 a lack of experience of pleasure, not a lack of motivation. 0:16:56.800 --> 0:16:59.080 And it wasn't until the eighties that some other people 0:16:59.120 --> 0:17:00.800 came along and they were like, no, oh, we've been 0:17:00.800 --> 0:17:02.360 getting this wrong all this time. 0:17:02.800 --> 0:17:06.960 Yeah, in the eighties they use sugar instead of meth amphetamine, 0:17:07.000 --> 0:17:10.280 I guess. And once again, very kind of cruelly, they 0:17:10.320 --> 0:17:15.360 cut off, they didn't allow them any dopamine. They killed 0:17:15.400 --> 0:17:17.760 them off with drugs. But this time they gave them 0:17:17.760 --> 0:17:21.840 the sugar and they said they're liking the sugar. You 0:17:21.880 --> 0:17:23.760 can tell by the look on that little guy's face, 0:17:24.280 --> 0:17:26.840 and he enjoys it. But and this is the key, 0:17:27.280 --> 0:17:29.280 it's not coming back and saying give me more sugar, 0:17:29.280 --> 0:17:30.440 Give me more sugar. 0:17:30.800 --> 0:17:32.920 Right, or give me more meth. 0:17:34.359 --> 0:17:34.639 Sure. 0:17:36.560 --> 0:17:39.280 So this whole thing, this changed our understanding, at least 0:17:39.280 --> 0:17:43.520 in the academia among people who study this kind of thing. 0:17:44.240 --> 0:17:47.160 We realized we were misinterpreting what we were seeing and 0:17:47.200 --> 0:17:51.360 that a lack of dopamine didn't lead to a lack 0:17:51.440 --> 0:17:56.520 of pleasure called an ahdonia or an hodonia. It was 0:17:57.640 --> 0:18:00.879 a lack of motivation to seek out that. That's the 0:18:00.920 --> 0:18:03.760 effect of not having enough dopamine that we found from 0:18:03.800 --> 0:18:06.840 those rat tests. So like this whole new framework of 0:18:06.920 --> 0:18:10.119 understanding it kind of came along because, to be clear, 0:18:11.000 --> 0:18:15.440 dopamine is very much associated with things that give us pleasure, 0:18:15.800 --> 0:18:19.239 and it does seem like the more pleasurable something is, 0:18:19.680 --> 0:18:22.840 the more dopamine gets released. Like, for example, I think 0:18:23.080 --> 0:18:25.600 I saw it like eating something that tastes really good 0:18:26.520 --> 0:18:30.280 increases your dopamine levels by one hundred percent sometimes yeah, 0:18:30.440 --> 0:18:35.160 but cocaine increases your dopamine levels ten times that. So 0:18:35.200 --> 0:18:39.119 the more intense the pleasurable experience is, the more dopamine 0:18:39.359 --> 0:18:42.600 gets released. So it's definitely associated with it. What they 0:18:42.680 --> 0:18:46.040 found is like the dopamine is not making you feel pleasure. 0:18:46.280 --> 0:18:49.960 There's something else involved. It's just it's never caught with 0:18:50.000 --> 0:18:52.520 the smoking gun, but it's always there when the dead 0:18:52.560 --> 0:18:55.320 body's found, and it has this mysterious smile on its 0:18:55.320 --> 0:18:57.879 face because I know you can't prove anything. 0:18:58.160 --> 0:19:01.679 Yeah, well, it's liking versus And that's a theory of 0:19:01.760 --> 0:19:07.399 reward behavior. Where liking is that pleasure that hits you 0:19:07.440 --> 0:19:10.880 get right when you put that bite of peanut butter 0:19:10.920 --> 0:19:14.080 pie in your mouth, is that pleasure. Wanting is the 0:19:14.119 --> 0:19:17.639 motivation to earn the reward that you get out of 0:19:17.680 --> 0:19:22.560 having that peanut butter pie. Like you know, you're up 0:19:22.600 --> 0:19:26.280 in the hotel room. They don't have room service, but 0:19:26.359 --> 0:19:27.840 you can get up out of bed, and you can 0:19:27.840 --> 0:19:31.120 get dressed, and you can get down the stairs because 0:19:31.119 --> 0:19:33.399 the elevator's broken and get that peanut butter pie if 0:19:33.400 --> 0:19:39.760 you want to. But dopamine isn't enough to motivate you 0:19:39.840 --> 0:19:42.480 to get up and go get that peanut butter pie necessarily, 0:19:42.520 --> 0:19:45.440 even though you have great, great memories of the taste 0:19:45.480 --> 0:19:47.800 of it on your tongue and you'd love that stuff. 0:19:47.640 --> 0:19:50.520 You're right. But if you do get up and go 0:19:50.560 --> 0:19:52.520 get that peanut butter pie, that means that in the 0:19:52.560 --> 0:19:56.320 past you've had peanut butter pie or have created an 0:19:56.359 --> 0:19:59.000 image of the peanut butter pie you've never had that's 0:19:59.040 --> 0:20:03.600 so great. The dopamine is produced in enough amounts to 0:20:03.600 --> 0:20:06.280 actually get you up out of bed, dressed and going 0:20:06.320 --> 0:20:08.520 down the stairs to get that peanut butter pie. They're 0:20:08.560 --> 0:20:09.600 related in that way. 0:20:10.280 --> 0:20:14.640 Yeah, absolutely, So it's not actually causing the pleasure. It's 0:20:14.720 --> 0:20:18.919 just influencing how your brain is taking all this stuff 0:20:18.920 --> 0:20:21.680 in basically, and there are a couple of different ways 0:20:21.680 --> 0:20:25.160 of looking at how this happens. There's one theory called 0:20:25.280 --> 0:20:30.240 a that it's prediction error, so you get more bang 0:20:30.480 --> 0:20:34.359 for your buck. Basically, you expected to like that peanut 0:20:34.400 --> 0:20:37.160 butter pie, but this was the best peanut butter pie 0:20:37.280 --> 0:20:40.240 you've ever had, maybe the best dessert you've ever had 0:20:40.280 --> 0:20:43.480 in your life, and you're like, wow, your brain says 0:20:43.800 --> 0:20:45.760 that was way way better than I thought it was 0:20:45.800 --> 0:20:47.840 going to be, so it reinforces. 0:20:47.200 --> 0:20:50.560 It right, And to put it in kind of computational terms, 0:20:51.440 --> 0:20:56.239 dopamine is a prediction error somehow that chemical measures the 0:20:56.359 --> 0:21:00.439 difference between what you expected and the amazing reward you got, 0:21:01.080 --> 0:21:04.400 and the greater the difference, the more pronounced a connection 0:21:04.520 --> 0:21:07.320 that dopamine is going to make between going and getting 0:21:07.359 --> 0:21:10.480 peanut butter pie and eating peanut butter pie, so you'll 0:21:10.520 --> 0:21:12.520 have more motivation to do it next time. 0:21:13.200 --> 0:21:16.200 Yeah. The other way of thinking about it is the 0:21:16.640 --> 0:21:21.280 dopamine itself is the motivational signal. So it's what makes 0:21:21.359 --> 0:21:23.879 me get out of that bed and put on my 0:21:23.960 --> 0:21:28.600 clothes and actually go down those stairs, because I'm motivated 0:21:28.640 --> 0:21:30.600 to go get that reward. 0:21:31.240 --> 0:21:34.280 Right, And this is where that Awakenings anecdote comes in. 0:21:34.680 --> 0:21:35.280 Let's hear it. 0:21:36.160 --> 0:21:38.560 So you were talking about how, you know, the peanut 0:21:38.600 --> 0:21:40.520 butter pie motivating you to get out of bed and 0:21:40.560 --> 0:21:47.000 actually go. That definitely jibes with research, particularly something reported 0:21:47.000 --> 0:21:49.520 by Oliver Sachs in the book and then later the 0:21:49.560 --> 0:21:56.280 movie Awakenings. There was an epidemic of something called encephalitic lethargia, 0:21:57.280 --> 0:22:00.320 which is what happened to Robert de Niro's character. Remember 0:22:00.400 --> 0:22:02.399 as a boy, he caught this thing and he just 0:22:02.480 --> 0:22:07.720 kind of frozen place. It's where you develop Parkinson's symptoms 0:22:07.720 --> 0:22:10.320 so much that you just don't you can't move. You 0:22:11.560 --> 0:22:16.600 cannot move. You have you don't have the required dopamine 0:22:16.920 --> 0:22:19.679 to actually move, so you're just sitting there, frozen in 0:22:19.720 --> 0:22:23.160 place like a statue. But anybody who saw this movie 0:22:23.400 --> 0:22:26.920 remembers being amazed by this scene. If a certain patient 0:22:27.040 --> 0:22:31.840 is stimulated, their dopamine is stimulated just enough, they can 0:22:31.840 --> 0:22:35.320 actually overcome that being frozen in place. And so there's 0:22:35.359 --> 0:22:38.520 a famous scene where Oliver Sax tossed one of the 0:22:38.520 --> 0:22:42.119 patients some oranges and she caught them like she was 0:22:42.119 --> 0:22:43.760 a frozen sets and all of a sudden she's catching 0:22:43.800 --> 0:22:47.920 oranges and then juggles with them. Or there's another patient 0:22:47.960 --> 0:22:51.119 that was on the beach, I believe in their wheelchair 0:22:51.280 --> 0:22:54.280 saw someone drowning and was motivated to get up and 0:22:54.320 --> 0:22:57.199 go save the person and then come back and go 0:22:57.320 --> 0:22:59.960 back to this frozen statue kind of stasis. 0:23:00.960 --> 0:23:01.600 Great scene. 0:23:02.400 --> 0:23:06.240 It is so like that has to do with the 0:23:06.280 --> 0:23:12.040 motivational aspect of dopamine, and that given the right stimulus, 0:23:12.680 --> 0:23:16.720 even something that tremendous as just a crazy amount of 0:23:16.720 --> 0:23:21.080