General Stuff I Blog About: Dopamine!

Oct 22 2008 Published by under Neuroscience

So this is the second installment for general information on the things I like to blog about. Today's topic: DOPAMINE
As you might be able to tell from many of my older and newer posts, I like dopamine. It's one of the transmitters I'm working on for my thesis, in fact. I've talked a little bit about dopamine as it relates to the stuff I blog about, but below I'm going to talk about it a little more. And of course, there's always wikipedia, but I don't really like the ways theirs is organized. Could I edit it? Sure I could. But I've got this laziness problem...

The major problem with trying to do a general post about dopamine is that there is so much out there on it. There's a ton of research going on on dopamine, including Parkinson's Disease, schizophrenia, obsessive compulsive disorder, attention deficit hyperactivity disorder, sleep cycles, and drug addiction, just to name a few. So I'm not going to get to everything there is about dopamine. I'll do my best just to give you the basics on where it comes from, where it goes, and some of the things it does, and though I can by no means cover everything, I will give it my best shot.
The Chemical
Looks like this:
(Courtesy of 3dchem, © Karl Harrison, which is GREAT place for looking at chemicals)
It's what we call a monoamine, which basically means it has one amine group (the bit with the blue ball on it, the blue ball is Nitrogen) as part of its structure. There are several monoamines in the brain, including dopamine itself, norepinephrine, and epinephrine. Your brain makes dopamine all the time, out of tyrosine molecules, which are one of the 20 major amino acids that you have that make up all the different proteins and things in your body. Knowing exactly how dopamine is made is actually pretty important, scientists tweak the dopamine pathway all the time to run experiments or treat disease symptoms.
Basically, tyrosine (your starting molecule) is transformed into another chemical called L-DOPA by an enzyme known as tyrosine hydroxylase. Tyrosine hydroxylase is the rate limiting step (basically, the slowest one) in the formation of dopamine, and so scientists often manipulate levels of tyrosine hydroxylase in animals to look at the effects on dopamine levels in the brain. You can also look at levels of tyrosine hydroxylase to see how much dopamine there is likely to be at any given time.
So tyrosine hydroxylase makes L-DOPA. L-DOPA is the molecule right before dopamine and is very well known as the drug Levodopa. This is the main treatment for Parkinson's Disease. See, the issue with dopamine is that it gets broken down in the body VERY quickly, and so if you take it as a pill or something, it would never get to the brain and help your symptoms. L-DOPA, however, doesn't get broken down in the body, instead it goes to the brain and is broken down there into dopamine, which is why you can take L-DOPA as a pill and get dopamine into your brain. L-DOPA is changed into dopamine via an enzyme known as aromatic amino acid decarboxylase (AADC), and then you have dopamine, ready to be stored and released as either a neurotransmitter or a hormone.
Dopamine the Neurotransmitter
For those of you who've been hearing me say "neurotransmitter" for the past few months and keep going "wha?", a neurotransmitter is a chemical signalling molecule in the brain. As I'm sure you know, brains are made of cells, and cells have to communicate with one another. They do this by sending signals. Within a cell, the signals move as electical waves along the cell membrane (called action potentials), but when it comes to signalling to another cell, they have to do something else. It's not considered polite to just go zapping your neighbor. So when a signal gets to the synapse (the junction where two cells meet), the signal is translated into a release of chemical from one cell (the presynaptic cell) to the other (the post-synaptic cell). I looked around on youtube, and one of the best videos I could find of this was here.

Though this is also awfully good, and includes a bit about why I blog about dopamine specifically:

When a neurotransmitter is released into a synapse, it crosses the tiny gap and binds to receptors specifically for it on the other side. In dopamine's case, we call these receptors D1, D2, D3, D4, and D5, which are just numbers assigned to the receptors with specific sequences in their protein structure. The receptor activation goes on to produce either a further action potential or to inhibit signalling, depending on the kind of cell and the receptor involved.
So we know now that dopamine is a signalling molecule. But not every cell has dopamine, and in fact dopamine is produced only in a few, very specific regions of the brain. The regions that I am concerned with are the Substantia Nigra and the Ventral Tegmental Area. The substantia nigra (latin for black substance) actually IS black. It looks like someone has been drawing little pencil lines near the base of your brain. The cells themselves are black because they contain high levels of melanin, which makes things very dark in appearance. The substantia nigra is located in an area of the brain called the midbrain. I guess this is the best picture for getting an idea of exactly where that is...
Dopamineseratonin%20brain.gif From Wikipedia. I really wish I had a fresh brain slice to show you. It looks so cool when you can see it in the midbrain right above the peduncles...
The substantia nigra is one of the main places in the brain which modulates (changes or affects) movement. It is famous for the degredation that takes place there to produce the symptoms of Parkinson's Disease, which include tremor, akinesia (an inability to move), and rigidity.
In that picture, you can also see the Ventral Tegmental Area, which we like to call the VTA. It's an area ths is right next to the substantia nigra, and one that I tend to like to blog about more. the VTA projects forward toward an area known as the striatum, and particularly to an area I like very much, the Nucleus Accumbens. This is an area of the brain which we think is very concerned with the concepts of motivation and the rewarding aspects of stimuli (it always amuses me that "stimuli" is basically the science term for "stuff"). Dopamine, which is sometimes known as the "pleasure molecule", increases in the nucleus accumbens when we get things that are "rewarding", such as sex, drugs (especially drugs), rock and roll, food, chocolate, pretty shoes, etc. Changes in dopamine signalling in the nucleus accumbens are thought to be linked to things like addiction. Of course, dopamine also goes other places, including the prefrontal cortex, which is thought to have a role in schizophrenia, ADHD, and obsessive compulsive disorder.
Dopamine as a Hormone
Dopamine also acts as a hormone which has its main effects in the hypothalamus. Here, release of dopamine inhibits the secretion of prolactin. Prolactin is a hormone which helps regulate orgasm and the release of milk during breast feeding. I don't tend to blog about this stuff so much, though the dopaminergic regulation of the refractory period after orgasm is pretty cool.
Dopamine Receptors and Transporters
A lot of research on dopamine signally focuses on the receptors and transporters involved. Luckily, there aren't very many actual receptors and there's only one transporter (though it comes in two different flavors), though between them they can have dizzying arrays of effects.

The dopamine transporter (DAT)

The DAT is a big molecule found on the pre-synaptic side of a synapse. It's dopamine's recycler. Dopamine needs to be released in sharp bursts, you don't want a signal hanging around and stimulating forever, so once dopamine is in the synapse, it is very quickly recycled by the DAT back up into the pre-synaptic cell, where it can be re-stored and used again. There are technically two kinds of DAT, DAT1 and DAT2, but most drugs don't differentiate, and so most things I'll talk about treat them as one.
The DAT is mostly well known because people believe that it is responsible for some of the effects of cocaine. Cocaine is a molecule that blocks the DAT, so dopamine cannot get recycled. Instead, it builds up in the synapse, stimulating the post-synaptic neuron over and over again, and causing lots of motor movement, focus, and euphoria. There are lots of other molecules out there which affect the DAT, including amphetamine (also know as Adderall), methylphenidate (also known as Ritalin, and while I must blog about extensively some day), methamphetamine (SCARY), and possibly even some of the effects of alcohol. Other drugs of abuse may not act directly on the DAT, but still have effects on the dopamine system, such as morphine, percoset, nicotine, and marijuana.
Dopamine receptors
There are five dopamine receptors, and luckily they all act in one of two ways! Unluckily, that does not make them at all less complicated.
DA D1 and DA D5: These are known as "stimulatory receptors", meaning they stimulate the cell that they are on when they get activated by dopamine. Now, if that cell is ALSO stimulatory to further cells down the line, the net effect is stimulation, but if the cell is inhibitory to other cells down the line, the net effect can be inhibition.
DA D2, D3, and D4: These are known as "inhibitory" receptors. But remember the main effect is not always inhibitory, unless they are inhibiting a stimulatory cell. They can also inhibit an inhibitory cell, which can stop inhibition of other cells down the like and result in stimulation! Does your head hurt yet?
There are lots of drugs out there (usually only used in experimental settings) which activate one or more of these receptors, so that we can see what the effects of any given receptor in any area of the brain are, though we still don't know half of all there is to know about these receptors.
That's where I'm going to leave the subject of dopamine right now. Believe me, you have no idea (I also have no idea) how deep the rabbit hole goes. But this should be enough to give you an idea of what dopamine is when I talk about it, and a little about how it works. Maybe next time I'll be brave enough to tackle serotonin! If you thought dopamine was complicated...

21 responses so far

  • laura says:

    good effort. just one thing; do you need to dumb it down so much? i mean, anyone who doesn't know that the brain consists of cells, probably also doesn't read this blog..
    on another note, i know everyone always focuses on the midbrain when it comes to DA, but aren't prefrontal effects much more interesting? would really love to see a post on that..

  • who's yer daddy says:

    I respectfully disagree, laura. I think Scicurious gets pretty techy pretty fast, leaving readers who don't understand brain physiology in the dust...

  • Michael says:

    I'm a pharmacist, so this is right up my alley, so to speak.
    I have always thought dopamine was the key to something I have observed-schizophrenics use cigarette smoking to blunt the side effects of psychotropics, and gamblers also tend to be smokers. Seems to me like there should be a link there. But correlation, causation, etc.

  • scicurious says:

    Laura: Sometimes I do have to dumb it down that much. I know of several people who read this blog who don't know much about science, so you have to be willing to give them the VERY basic. Of course we all know our brains are made of cells, it's just a good starting off point. I really want to make people who may not be "sciency" by nature interested, and to get them to realize that this is stuff that anyone can learn, and to do that you sometimes have to start basic. And people who already know the basic stuff can just scroll down. 🙂
    And prefrontal? That is a WHOLE can of worms. I've been reading a lot about prefrontal dopamine and ADHD medications lately. I don't know if I'll be able to do a post on it in the near future, but I can try. And I like your blog, btw, excellent reference lists!
    Michael: Yeah, I'm a little familiar with that literature on schizophrenia and smoking. Apparently most of them are smokers prior to medication as well, I heard something about a theory of changing dopamine and glutamate signalling to the prefrontal cortex that way...
    The gambling and smoking, hey, they're both kind of addiction, right? It's like any other two drugs, you're never going to find an addict who JUST does cocaine and nothing else, they are also alcoholics, many are smokers, some do marijuana, it's never just one thing.

  • ScottK says:

    I for one think this was a wonderful post. Just the right mix of technicality and winsomeness. I like the nucleus accumbens too, primarily because I'm an addict in recovery, so I think about it a lot.
    Thanks for the post, scicurious. Don't know if it did much for my dopamine levels, but it helped my serotonin quite a bit.

  • Brian says:

    I think the articles are great. I just started reading this blog about a month ago and I appreciate the mix of technical and nontechnical explanations.
    I do like the suggestion you mentioned previously about writing some background articles and referring to those in more technical articles for those who need the extra explanation.

  • Mike says:

    Good overview. I don't a post a while back about the issue of dopamine being involved in pleasure. It's a somewhat controversial issue with not all researchers agreeing that it is correlated with pleasure (likeing vs. wanting).
    I think D1 receptors in the prefrontal cortex are an interesting topic. They are associated with executive functioning. They also seem to be associated with negative schizophrenic symptoms and ADD. There's a D1 receptor enhancer in the pipeline that I have my eye on.
    I think it might be a very useful cognitive enhancer, if it actually gets FDA approval.
    The wikipedia article on dopamine really needs someone who is an authority on dopamine. It has a lot of inaccuracies in it.

  • Mike says:

    That last post should read; Good overview. I *did* a post a while back.... Not sure where the *don't* came from.

  • Chris says:

    Where might one read about the refractory period and its interaction with dopamine? I'm mildly curious since I managed to completely eliminate the refractory period during my college days experimenting with di-isopropyl-tryptamine (I hope I spelled it right). No longer the experimenting tpwe that I was, it's a lingering curiosity nonetheless.

  • scicurious says:

    Mike: oy. The liking vs wanting debate. We can spend hours on this, along with reward vs reinforcement. The problem is trying to keep it in relatively simple terms. I usually think of it in terms of motivation, but even that is up for debate. I haven't read anything lately on D1 in the prefrontal cortex, got any refs I can look at? I could use some.
    Chris: try here or here
    if you're up for some heavy sciencespeak. I actually don't know a lot about it myself, it's not one of my major interests, but I could do a post on it if you're really curious.

  • I think dopamine researchers are definitely trending away from the word pleasure.

  • DrugMonkey says:

    Changes in dopamine signalling in the nucleus accumbens are thought to be linked to things like addiction.
    Given that substantial fractions (probably the majority) of the people exposed to "stuff" get the acutely pleasurable part without going on to develop addiction...
    What does the acute rewarding / pleasurable effect of drugs or other stimuli have to do with addiction itself?

  • scicurious says:

    DrugMonkey: ouch. Such questions so early in the morning. You're absolutely right (as you always are), and people have been searching for years for the difference between a guy who does coke and goes on to be president, and one who ends up in a back alley giving hand jobs for his next hit. I certainly don't know anywhere close to everything about it, I am but a lowly grad student. I've found this blog has been incredibly good for highlighting all the stuff I don't know. There are a couple of ideas I can give off the top of my head, but really I may have to do more reading and write a post on it. Can I ask you for advice on it?
    First off: Dopamine in the accumbens is though to be the "kick start" for addiction. Once addiction is really underway, signalling shifts to places like the dorsal striatum, which is involved in habit patterns, the orbitofrontal cortex, for drug-related cues, and the prefrontal cortex, for impairing higher function. Dopamine may be responsible for the initial positive reinforcement of drugs that makes you come back a second time, and a third time, but after a while other things take over.
    Other things:
    1) There are ideas of positive vs. negative reinforcement. I don't feel like this really works for cocaine, but alcohol makes a good example. The "rewarding" properties are at first what make people come back for more drinks. But then there are properties of "negative reinforcement", which are things like your hangover. As you drink more, the negative properties will begin to override the positive ones, and you will start to drink just to avoid the feelings you have when you're in withdrawal.
    2) There are changes in people's brains when they go from using recreationally to using as a habit. Nora Volkow, head of NIDA, has some work on this, especially work on changes in DA D2 receptors. There are implications that, the more cocaine you use, the more your brain gets used to the cocaine being there, receptors desensitize, and you get decreases in firing, resulting in chronic low dopamine when the drug is not onboard. Chronic low dopamine is hypothesized to feel icky. Thus you will take more drug, more often, just to feel "normal". So the more you do a drug like cocaine, the less it is about "pleasure" or "reinforcement" or "reward", and the more it's about maintaining a state. The problem with this one is that it's very hard to find people who are willing to get their brains scanned on coke and don't have a coke habit. And we can't do before and after pics before someone gets addicted to cocaine. I know Mike Nader, out of Wake Forest University, has been trying to do this in monkeys, look at D2 receptor levels and then see how much coke they do, as well as how the dopamine system changes during and after administration
    3)Dopamine is obviously not the only neurotransmitter involved. There are changes in responses to "rewarding" stimuli that are linked to glutamate, the negative properties of ethanol are linked to changes in GABA, and I'm sure there's a role for serotonin.
    4)There may be genetic predispositions, or predispositions that appear as responses to environment. For example, a monkey who's at the bottom of the social ladder will do a lot more coke and find the coke more rewarding than the monkey who's getting all the grooming and girls. And the monkeys at the bottom have different levels of DA D2 than monkeys at the top. So perhaps in some people, there could be responses to environmental stimuli which make them more likely administer drugs, and make them more likely to go back.
    Yeah, I really need to read up and do a post on this. Do you have any thoughts? Please call me out if I'm wrong! I don't learn otherwise.

  • DrugMonkey says:

    very nice response, scicurious! and I'm being a bit of an ass, of course. this is the major divide across which the field splits. You can guess on which side I trend...
    The National Institute on Dopamine (What did you think "NIDA" stood for?) is gradually coming around to the notion that maybe they need to pay attention to some other stuff but it is hard to turn the QE2 around all at once.
    Still, it is really, really (really) important for grad students who may be being trained in departments which continue to focus nearly exclusively on the theoretical side of "it's all about the acute reinforcing effects" to understand that when it comes to solving
    addiction this is an epic FAIL strategy. Or at the very least for you to understand that this may be completely irrelevant for addiction per se.

  • Mick says:

    Good post. Now do seratonin.

  • Mike says:

    Here's a paper about D1 receptors in the prefrontal cortex and their relationship to cognition. It mostly talks about schizophrenia.
    As to dopamine's role in pleasure. I definitely think that increasing dopamine can enhance a person's pleasure. Dopamine receptor agonists can decrease anhedonia.
    Dopamine doesn't make food taste any better, though. While mu-opioid receptor activation in key brain areas makes food subjectively tastier.
    That's where the liking vs. wanting comes into play. Both opioid and dopaminergic drugs are rewarding, but only opioids make food taste subjectively better.

  • Tom Michael says:

    Check out this link for a detailed discussion on the Dopamine system as an anticipating reward mechanism rather than a pleasure system:
    Also remember that Dopamine has multiple roles. Think about the effect of L-Dopa in parkinsons patients on movement for example. Neurotransmitters can have multiple effects depending on the system they are involved in (reward anticipation, movement etc...) and the receptor subtype. This can explain for example how Dopamine system disfunction is responsible for both positive and negative symptoms in Schizophrenia for example.

  • Donna B. says:

    I appreciate dumbed down stuff! I'm a layperson who has been reading about the brain ever since my son suffered a severe closed-head injury in the early '80s. So, I'm not completely science illiterate, just mostly 🙂
    What has always been striking to me is how the media discovers discoveries or at least what they call discoveries and announce them as the final word on something.
    My son had diffuse injuries, but one area where a notable injury was identified was the substantia nigra. Not having the internet back then, I took the radiologist's report with me to the medical school library. I remember being shocked at the interior location of that injury. It reinforced for me how lucky we were that he is only partially paralyzed, has tremors, rigidity, and depression.
    I'm sure a similar injury would have been fatal only a few years before.
    Thank you for an informative article on dopamine.

  • Ares Vista says:

    I also enjoy dope-o-mine!

  • Domain Names says:

    Wow, this is some complex stuff - great post & pics.