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Welcome to Stuff You ShouldKnow, a production of I HeartRadio.
Hey and welcome to thepodcast.
I'm Josh and there's Chuck and Jerry's heretwo, three amigos back together again after some massively triumphant liveshows.
Yeah, we did our little northeast springswing.
Yeah. And it wasgreat. This is a goodshow.
Whichone? The podcast topic that we didlive.
Oh, I gotit. That we're doing allyear.
I gotit. It was prettygood.
I love thattopic. That's what you call anon-sequitor.
But it does feel good to beback.
Doesn't it back in thestudio, back doing what we're born todo?
I kind of prefer onstage, butsure.
This is greattoo. Do you like the thrill of theaudience, the roar of thecrowd, that bowl running atyou?
Yeah.Nice. I like it too sometimes when I'm not totally terrified because I drank too much energydrinks.
Well, the wonder if your dopamine receptors are functioning as theyshould.
Yeah, that's a greatquestion,Chuck.
And that's a wonderful segue too because it just so happens thattoday, the topic of this episode isdopamine.
And there's probably no more misunderstoodneurochemical, certainlyneurochemical, maybe substance in your body at all thandopamine.
We used to think we had a really great handle on dopamine and what it does and how itworks.
And it turns out that we are every turn a new study comes along thatsays,nope, we'rewrong.
Yep, we're wrong aboutthat.
Well, whatabout,yep, wrong aboutthat.
Basically, everything we know in popularculture.
And Imean, if you've even gone to Cleveland Clinic website or WebMD website or Harvard Health has somearticles, you'll see this old antiquated outdated view of what dopamine is being kind of paradedaround.
The idea that it's a pleasure inducing chemical that if something gives youpleasure, you're responding to a hit of dopamine and that is just absolutely nottrue.
Yeah, and this may be the most oft-covered stuff you should know thing that hasn't gotten its own titleyet.
Yeah,man, dopamine is the raining champ rightnow.
Yeah, we talk about this stuff all thetime.
It seemslike.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 justpleasure.
Likeeverybody,yes, it is associated withpleasure, just not the way we've thought for verylong.
And it does a lot of other stufftoo.
Essentially, what it does is it signalsthings.
Itsays,hey,you, you behave or you actup, you stopbehaving.
Something likethat. I'm not quite sure exactly what itsays.
I don't speakdopamine, but it's aneurotransmitter.
So it's a chemical messenger in the brain atbase, but it's associated with so many different thingsthat, ofcourse, dopamine comes up all the time in ourpodcast.
It suredoes. So itis, like yousaid, aneurotransmitter, one of more than a hundred of those bad boys functioning in ourbodies.
Andit, like yousaid, it lets thingscommunicate.
It's afacilitator, but it gets all the press forit's, youknow, like the feel good stuff that youmentioned, addictionbehaviors, whether it's gambling or drugs or the thrillof, youknow, those people that walk around on ledges andstuff.
Ledgewalkers?Yeah, ledwalkers.
But it does all kinds ofthings.
That's just where it makes the the newspaperheadlines.
But we should probably talk a little bit about just the neurotransmitter cycle that it goesthrough.
Sure. So the whole thingstarts.
It turns out that dopamine is used throughout thebody, but the in for the mostpart, it's used in thebrain.
The problem is is if you like had a big handful of dopamine and you just shoved it in yourmouth, it couldn't make it into your brain foruse.
It can't cross the blood brain barrier in otherwords.
Fortunately, the thing that makes dopamineup, it's essentialingredient, tyrosine and amino acid can cross the blood brainbarrier.
And when it getsthere, it gets a big fat hug from something called tyrosinehydroxylase.
And that converts it into dopamine and all of a sudden your brain'slike,yes, let'sgo.
That'sright. And we've known about it a longtime, it's been around a longtime.
It is not exclusive to humanbeings.
No, that's a bigone.Yeah, it's in all kinds ofanimals.
But we are really kind of great at makingit.
And I was about to say hooked onit, but that implies the whole addictionthing.
And I don't want to go down thatroad.
But humans love the stuff and we produce about three times as much as other primatesdo.
Yes. And infact, Emily Deane's wrote an article in2011, I think on psychologytoday, she's an evolutionarypsychiatrist.
And she said that dopamine is what made humans sosuccessful.
And from what I cantell, the latest research about dopamine is that it essentially is what allows us to learn about the world aroundus.
We make connections that collectively form our mental map of the world of how we're to behavior on other people of how we do things like go getfood, like that dopamine is somehow behind all ofit.
And that because we're so responsive todopamine, and we produce so much dopamine compared to other animals in the animalkingdom, that is conceivably what has allowed us to become as successful as we are compared to otheranimals.
And thatnuts, like it could all just come down to dopamineessentially.
Yeah. And opposable thumbsmaybe?
Sure. But Imean, what are opposable thumbs if you can't have get the where with all the to moveit?
True. But if you had the where with all to moveit, you couldn't grabsomething.
Yes, you can use the heels of bothhands, just like athumb.
Are you under selling the opposablethumb?
Yes. I'm sick of the opposable thumb always hogging thespotlight.
It's dopamine'stime. You can get thoseremoved, youknow.
See how youdo. That sounds like a dare tome,Chuck.
Say goodbye to your tennisgame.
I can play it just by holding the racket with both heels of myhand.
Or I guess we should have saidpickleball.
It'd be morecurrent,right?
I don't playpickleball.
I haven't tried ityet. I want tothough.
Okay.Well, there's plenty of places and people to play it with yet I have found no one or noplace.
Oh, I'm sure somebody will write in an offer to play withyou.
Ofcourse. Then I go out there and I like blow my ACL orsomething.
That wasnice. So at the highestlevel, youknow, we kind of talked about this a thousand timesbefore, but dopamine functions as aneurotransmitter.
It enables signals to pass through thesegaps, these synapses and make connection from neuron toneuron.
That's just sort of the bird's eyeview.
But there are all kinds of things that dopaminedoes.
Depending what kinds of neurons it's talking to and it's introducing to oneanother, it's going to have different effects on the humanbody.
Yes. So there's D1 toD5, Ithink, types ofreceptors, dopaminereceptors.
And four pathways that theyfollow.
And like yousaid, depending on what receptors being activated and what pathways beingfollowed, all sorts of different stuff canhappen.
Dopamine is associated with motorcontrol,learning,memory, malfunctions in it can result inpsychosis.
They use dopamine as a vasostimulant to treat heartconditions.
It has just a cluster of different effects on thebody, depending on where it's beingprocessed, like what pathway it's beingprocessed.
And I think that there's four of themtotal.
Did you want to talk aboutthis?
I feel like weshould.Okay.
The first one is the Nygros triadaltract.
You mentioned motor controlfirst, and that's the tract that has to do with motorcontrol.
Yeah. So if those aren't workingcorrectly, the one that dopamine neurons are the dopamine-ergic pathway in the Nygros triadaltract, that can result inParkinson's.
It's very famously associated with dopamine for anybody who has read Awakening's or saw themovie.
Yeah. Which we'll probably talk about a little bit morelater.
Thatmovie?Yeah.Okay.
I got agreat, great bit up mysleeve.
Okay. The second pathway is a mezzo corticolpathway.
That has a lot to do with executivefunctioning, prioritizingstuff, how your brain plansthings, how it files awaystuff, and howit, youknow, how it organizes your overall sort ofpriorities.
Yes. And now it's time to talk about the most random dopamine-ergic pathway ofall, the tubero-in-fundibularpathway.
tubero-in-fundibular.
Yeah. I think you had it right the firsttime.
Okay. We'll edit out the secondone.
I'll put in a slide whistle overit.
So that connectsthis, the hypothalamus in the pituitarygland, and it's from what I cantell, I waslike,well, what else does itdo?
It's the sole role of this pathway is to block the production ofmilk, orto,yes, to prevent the production of milk in the female breast ofmammals.
That's what itdoes. That'sthat,well, that's that pathway'srole.
And if you block thatpathway, the milk productionbegins.
Isn't thatinteresting?
Yeah. We talked about that in thetwo-parter, the old breast feedingtwo-parter.
Oh, wedid?Oh,yeah.Oh, I don't rememberthat.
Yeah,yeah.Wow. You got a greatmemory.
No, I have a terriblememory.
I know you're making fun ofme.
There's, there's also the mesolimbicpathway.
We've talked a lot about the limbic system in theepisode, in manyepisodes, but reward andemotion.
And this is the one where this is the one that gets all the press because this is the one that has to deal withaddiction.
Pleasure. And we're going to talk a lot about reward and how reward factors end to how dopamineworks.
Right. This is the reason why some people get the chemical drawing of the molecular drawing ofdopamine, like tattooed on their wrists because they're so hedonic and intopleasure.
That's why you might see somebody with that because of thatpathway.
I never heard ofthat.Yeah, it's athing.
Unfortunately, it turns out to be amisinterpretation, but it is a thing that people dosometimes.
Sure.So, youknow, we talked about misunderstandings aboutdopamine.
And up until not too longago, we didn't know a lot about exactly how dopamine worked in thebody.
And there was a misguided thought that there was something called volume transmission atwork, which was you just sortof,well, you don'tflood.
We'll talkabout, youknow, artificially floodingdopamine, which is also a problem that resulted from thismisnomer.
But dopamine just went veryslowly.
It was not very specific atall.
Just kind of washed over thebrain.
And if it made some connections with variousneurons, then that was kind of the dumb luck of dopamine because dopamine is justdopey.
Right. Here's a great example of just how wrong we gotdopamine.
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 volumetransmission.
It could not be more opposite than the idea that just floods slowly across the brain and whatever it runs into it runsinto.
We found that inmilliseconds, a precise squirt of dopamine hits exactly the right neuron and exactly the right places right on themoney.
That's how dopamine isexcreted.
The exact opposite of volumetransmission.
Yeah. And we learned that not too longago, 2018 medical researchers at Hobbid released this paper andsaid,hey, guesswhat,everyone?
It's the opposite of everything you've been saying and everyonewent,oh,okay, sorry aboutthat.
Sure. Mightbe. So after the dopamine is excreted and it does itsjob, it actually breaks down remarkablyquickly.
It turns into something to metabolize into something called homovanilicacid.
Right. And from what I cantell, I don't know what the homo does to the vanillaacid, butvanilla, vanilla acid is the flavor ofvanilla.
So from what I cantell, if you tastedthe,the, the homovanilicacid, which is like the metabolite found in cerebrospinal fluid that we test to see how much dopamine you have in your brain at any giventime, it may taste likevanilla.
Wow. Isn't thatinteresting?
It'sgross. It isgross.
And I don't know also if we said that just 20,000 neurons are capable of synthesizingdopamine, but that's a really small proportion of the total number of neurons we have to about a hundredbillion, Ithink.
Yeah,absolutely. You want to take abreak?
Yeah, we'll break and we'll talk aboutwell, what everyone wants to hearabout, which is how dopamine and pleasure hold hands with oneanother.
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So check this wholeundersh- I should say misunderstanding of dopamine as the ultimate pleasurechemical.
If you take a drag off acigarette, if you snort a line toCoke, if the person youlove, like touches yourhand, if you get like an A from theteacher, like you're going to get a hit of dopamine and that's what your rewardis.
It's prettyold. It's an oldidea.
At least it dates back to the middle of the 20thcentury, which is we're getting further and further awayfrom, which makes megulp.
But that idea being discredited is pretty oldtoo.
Like it didn't last verylong.
The problem is its legacy stuck around for a really long time is still aroundtoday.
Yeah, forsure. There was a researcher speaking of old named James Olds in the 50s and 60s who did some experiments with rats andsaid,hey, every time I give these rats a little electrical stimulation in just the right place right there behind theear, they're going to keep pulling that lever down or whatever act I'm making themdo.
