The mesolimbic/mesocortical dopamine system, a passage from Behave, by Robert Sapolsky
(As a note before the passage, I'm transcribing this both in an effort to remember it better, rather than just looking up the associated words in a Kindle version of the text, and secondarily because it's the most visceral description of a phenomenon of rate-decreasing pleasure in repeated, wonderful experience that I've seen. It makes sense, I sympathize with my own biology as I feel a sense that there's nothing I can do but carry on, or limit peak rewards. Plus, I want to share it with you, who may never buy the full book. I'll use bold over sections I particularly resonated with, but otherwise the text is reproduced faithfully.)
Reward, pleasure, and happiness are complex, and the motivated pursuit of them occurs in at least a rudimentary form in many species. The neurotransmitter dopamine is central to understanding this.
Nuclei, Inputs, and Outputs
Dopamine is synthesized in multiple brain regions. One such region helps initiate movement; damage there produces Parkinson's disease. Another regulates the release of a pituitary hormone. But the dopaminergic system that concerns us arises from an ancient, evolutionarily conserved region near the brain stem called the ventral tegmental area (henceforth the "tegmentum").
A key target of these dopaminergic neurons is the last multisyllabic brain region to be introduced in this chapter, the nucleus accumbens (henceforth the "accumbens"). There's debate as to whether the accumbens should count as part of the limbic system, but at the least it's highly limbic-ish.
Here's our first pass at the organization of this circuitry:
- The tegmentum sends projections to the accumbens and (other) limbic areas such as the amygdala and hippocampus. This is collectively called the "mesolimbic dopamine pathway".
- The tegmentum also projects to the PFC (but, significantly, not other cortical areas). This is called the "mesocortical dopamine pathway." I'll be lumping the mesolimbic plus mesocortical pathways together as the "dopaminergic system," ignoring their not always being activated simultaneously.*
- The accumbens projects to regions associated with movement.
- Naturally, most areas getting projections from the tegmentum and/or accumbens project back to them. Most interesting will be the projections form the amygdala and PFC.
As a first pass, the dopaminergic system is about reward--various pleasurable stimuli activate tegmental neurons, triggering their release of dopamine. Some supporting evidence: (a) drugs like cocaine, heroin, and alcohol release dopamine in the accumbens; (b) if tegmental release of dopamine is blocked, previously rewarding stimuli become aversive; (c) chronic stress or pain depletes dopamine and decreases the sensitivity of dopamine neurons to stimulation, producing the defining symptom of depression--"anhedonia," the inability to feel pleasure.
Some rewards, such as sex, release dopamine in every species examined. For humans just thinking about sex suffices.** Food evokes dopamine release in hungry individuals of all species, with an added twist in humans. Show a picture of a milkshake to someone after they've consumed one, and there's rarely dopaminergic activation--there's satiation. But with subjects who have been dieting, there's further activation. If you're working to restrict your food intake, a milkshake just makes you want another one.
**footnote: And, in a fact that hints at a world of sex differences, dopaminergic responses to sexually arousing visual stimuli are greater in men than in women. Remarkably, this difference isn't specific to humans. Male rhesus monkeys will forgo the chance to drink water when thirsty in order to see pictures of--I'm not quite sure how else to say this--crotch shots of female rhesus monkeys (while not being interested in other rhesus-y pictures).
The mesolimbic dopamine system also responds to pleasurable aesthetics. In one study people listened to new music; the more accumbens activation, the more likely the subjects were to but the music afterward. And then there is dopaminergic activation for artificial cultural inventions--for example, when typical males look at pictures of sports cars.
Patterns of dopamine release are most interesting when concerning social interactions. Some findings are downright heartwarming. In one study a subject would play an economic game with someone, where a player is rewarded under two circumstances: (a) if both players cooperate, each receives a moderate reward, and (b) stabbing the other person in the back gets the subject a big reward, while the other person gets nothing. While both outcomes increased dopaminergic activity, the bigger increase occurred after cooperation.
Other research examined the economic behavior of punishing jerks. In one study subjects played a game where player B could screw over player A for a profit. Depending on the round, player A could either (a) do nothing, (b) punish player B by having some of player B's money taken (at no cost to player B), of (c) pay one unit of money to have two units taken from player B. Punishment activated the dopamine system, especially when subjects had to pay to punish; the greater the dopamine increase during no-cost punishment, the more willing someone was to pay to punish. Punishing norm violations is satisfying.
Another great study, carried out by Elizabeth Phelps of New York University, concerns "overbidding" in auctions, where people bid more money than anticipated. This is interpreted as reflecting the additional reward of besting someone in the competitive aspect of bidding. Thus, "winning" an auction is intrinsically socially competitive, unlike "winning" a lottery. Winning a lottery and winning a big both activated dopaminergic signaling in subjects; losing a lottery had no effect, while losing a bidding war inhibited dopamine release. Not winning the lottery is bad luck; not winning an auction is social subordination.
This raises the specter of envy. In one neuroimaging study subjects read about a hypothetical person's academic record, popularity, attractiveness, and wealth. Descriptions that evoked self-reported envy activated cortical regions involved in pain perception. Then the hypothetical individual was described as experiencing a misfortune (e.g., they were demoted). More activation of pain pathways at the news of the person's good fortune predicted more dopaminergic activation after learning of their misfortune. Thus there's dopaminergic activation during schadenfreude--gloating over an envied person's fall from grace.
The dopamine system gives insights into jealousy, resentment, and insidiousness, leading to another depressing finding. A monkey has learned that when he presses a lever ten times, he gets a raising as a reward. That's just happened, and as a result, ten units of dopamine are released in the accumbens. Now--surprise!--the monkey presses the lever ten times and gets two raisins. Whoa: twenty units of dopamine are released. And as the monkey continues to get paychecks of two raisins, the size of the dopamine response returns to ten units. Now reward the monkey with only a single raisin and dopamine levels decline.
Why? This is our world of habituation, where nothing is ever as good as that first time.
Unfortunately, things have to work this way because of our range of rewards. After all, reward coding must accommodate the rewarding properties of both solving a math problem and having an orgasm. Dopaminergic responses to reward, rather than being absolute, are relative to the reward value of alternative outcomes. In order to accommodate the pleasures of both mathematics and orgasms, the system must constantly rescale to accommodate the range of intensity offered by particular stimuli. The response to any reward must habituate with repetition, so that the system can respond over its full range to the next new thing.
This was shown in a beautiful study by Wolfram Schultz of Cambridge University. Depending on the circumstance, monkeys were trained to expect either two or twenty units of reward. If they unexpectedly got either four or forty units, respectively, there'd be an identical burst of dopamine release; giving one or ten units produced an identical decrease. It was the relative, not absolute, size of the surprise that mattered over a tenfold range of reward.
These studies show that the dopamine system is bidirectional. It responds with scale-free increases for unexpected good news and decreases for bad. Schultz demonstrated that following a reward, the dopamine system codes for discrepancy from expectation--get what you expected, and there's a steady-state dribble of dopamine. Get more reward and/or get it sooner than expected, and there's a big burst; less and/or later, a decrease. Some tegmental neurons respond to positive discrepancy from expectation, others to negative; appropriately, the latter are local neurons that release the inhibitory neurotransmitter GABA. Those same neurons participate in habituation, where the reward that once elicited a big dopamine response becomes less exciting.
Logically, these different types of coding neurons in the tegmentum (as well as the accumbens) get projections from the frontal cortex--that's where all the expectancy/discrepancy calculations take place--"Okay, I thought I was going to get 5.0 but got 4.9. How big of a bummer is that?"
Additional cortical regions weigh in. In one study subjects were shown an item to purchase, with the degree of accumbens activation predicting how much a person would pay. Then they were told the price; if it was less than what they were willing to spend, there was activation of the emotional vmPFC; more expensive, and there'd be an activation of that disgust-related insular cortex. Combine all the neuroimaging data, and you could predict whether the person would buy the item.
Thus, in typical mammals the dopamine system codes in scale-free manner over a wide range of experience for both good and bad surprises and is constantly habituating to yesterday's news. But humans have something in addition, namely that we invent pleasures far more intense than anything offered by the natural world.
Once, during a concert of cathedral organ music, as I sat getting gooseflesh amid that tsunami of sound, I was struck with a thought: for a medieval peasant, this must have been the loudest human-made sound they ever experienced, awe-inspiring in now-unimaginable ways. No wonder they signed up for the religion being proffered. And now we are constantly pummeled with sounds that dwarf quaint organs. Once, hunter-gatherers might chance upon honey from a beehive and thus briefly satisfy a hardwired food craving. And now we have hundreds of carefully designed commercial foods that supply a burst of sensation unmatched by some lowly natural food. Once, we had lives that, amid considerable privation, also offered numerous subtle, hard-won pleasures. And now we have drugs that cause spasms of pleasure and dopamine release a thousandfold higher than anything stimulated in our old drug-free world.
An emptiness comes from this combination of over-the-top nonnatural sources of reward and the inevitability of habituation; this is because unnaturally strong explosions of synthetic experience and sensation and pleasure evoke unnaturally strong degrees of habituation. This has two consequences. First, soon we barely notice the fleeting whispers of pleasure caused by leaves in autumn, or by the lingering glance of the right person, or by the promise of reward following a difficulty, worthy task. And the other consequence is that we eventually habituate to even those artificial deluges of intensity. If we were designed by engineers, as we consumed more, we'd desire less. But our frequent human tragedy is that the more we consume, the hungrier we get. More and faster and stronger. What was unexpected pleasure yesterday is what we feel entitled to today, and what won't be enough tomorrow.
(the book continues)