But dopamine is just the gateway neurotransmitter, the trigger. Dopamine is akin to the foreplay before sex (which also releases dopamine): the experience isn’t quite complete until the consummation, the euphoria, the pleasure—which is mediated through another set of chemicals, the endogenous opioid peptides (EOPs), whose cell bodies are in the hypothalamus, the brain area that controls hormones and emotions.15 The most famous of these is beta-endorphin, the brain peptide with properties similar to morphine. It binds to the same opioid receptor as does morphine or heroin, generating the pleasure signal in the nucleus accumbens (NA). The opioids are the business end of the reward pathway, and you can get there with opiate drugs such as hydrocodone (Vicodin) or oxycodone (OxyContin), or with your own beta-endorphin, which is released in response to vigorous exercise. This is what elite athletes try to achieve with long-distance running, to get that runner’s high.16 It has been shown that the pain relief associated with acupuncture is due to EOPs being released in the reward center. EOPs and opiate drugs bind to their receptors to create the sensation of pleasure. But guess what? Just like with dopamine, those EOP receptors are also down-regulated with chronic exposure, to limit their action as well (see Chapter 5), although we’re not sure what happens with runners.
First the motivation, then the consummation. First the desire, then the pleasure. But that’s assuming that your brain already knows what’s coming. Our behaviors that typify motivation and consummation are pretty much the same from person to person, but the experiences that trigger them are as individual as you are. What floats your boat may sink someone else’s, and vice versa. But you don’t know what trips your trigger till you’ve cocked the pistol. You don’t know what you like or want or need until you’ve experienced it firsthand—at least once. Take a rat naïve to cocaine, morphine, or sugar and implant a recording electrode into the VTA. Then give it a lever for drug administration. Prior to the first exposure, the rat doesn’t care about the lever and those dopamine neurons are quiet. But after that first hit, the reward signal is registered and that neuron is now primed for action. After that, just provide a cue (like the golden arches of McDonald’s) and those dopamine neurons will now fire at fever pitch.17 The rat will push that lever nonstop.
As a personal example, when I was a pediatric resident, I was hospitalized for a gastric ulcer after a bout with a toxic chicken curry. The ER doctor gave me a standard dose (15 mg) of meperidine (Demerol), and I was flying. My receptors had never experienced anything like it and had no idea it was coming. I never wanted to come down off that high. Harry Potter must have felt this way when he got his first broom. That single experience explained to me the power these neurochemicals have in shaping and changing the motivation and behavior of myriads of people. The problem is that EOPs and their drug counterparts, the opiates, also down-regulate their receptors through the law of mass action. And when opioid receptors down-regulate, you go from wanting to needing. That’s the neurochemical equivalent of addiction.
If You Scratch You’ll Keep Itching
The goal of reward is not in the motivation; it’s in the consummation. Activating those opioid receptors is where the action is. Pleasure is the goal. Desire is the driver. Motivation drives the outward behavior; consummation is the inward expression of reward.
Let me give you an example of how the reward pathway works for us—and against us. As I’m writing this, I’m in an Airbnb apartment in Paris (I know, rough draw, but somebody’s got to do it), but it’s August, it’s 95 degrees Fahrenheit with 90 percent humidity, it’s a three-hundred-year-old building, and there’s no air-conditioning and no ventilation. I’m sticky and I’m stuck in this flat writing, waiting for my wife to return from the Louvre with our kids. Right now I’m thinking of a grande coupe of chocolate ice cream. That’s my dopamine telling me to go down to the patisserie on the corner to get a big bowlful, because I deserve it. I could instead get a bottled water to correct my dehydration and to reduce my body temperature somewhat. Cold water can fix my physiology, but I’m not in this for physiology. I’m in this for reward. I’m writing, I’m stressed, I’m hot—and I really want some ice cream. I don’t need it, but I want it—and bad. That’s motivation—that’s the dopamine talking. I order two scoops—the hazelnut and the pistachio (chocolate is so Americain, I decide). Upon my first bite, I get this amazing feeling approaching gustatory nirvana. That’s the beta-endorphin, now giving me my food orgasm in my NA. I’m tempted to order a third scoop, but abstain. My wife returns from her excursion through the Renaissance and says, “Two scoops? Really?” At least I didn’t get three—would I have gotten 50 percent more pleasure from three than from two? More to the point, did I get double the pleasure from two than I would have had from one? That was the cortisol from the stress, shifting my dose-response curve to the right—a very common sequel to the motivation-consummation paradigm, which yields even more untoward effects than the ice cream itself (see Chapter 4). What is my reaction to my wife’s disdain? More cortisol from stress and a rightward shift on the bell-shaped curve. Time for a chocolate croissant.
In summary, reward comes in two phases in tandem: (1) motivation or desire (dopamine from the VTA impacting the NA), and (2) consummation or pleasure (EOPs from the hypothalamus impacting the NA and other areas of the brain). Dopamine is the trigger, EOPs are the bullets. You need both to fire the gun, unless someone else fires the gun for you (like the Demerol in the emergency room). EOPs are also designed to shut down further dopamine transmission to the NA, because, ideally, once your reward has been consummated, you don’t need any further anticipation. Cock the trigger, fire the bullet, hit your target, and win the stuffed animal at the fair. Unless . . . you never hit the target. This happens if the signal of either the dopamine or the EOPs isn’t effectively transmitted at the NA because of chronic overstimulation and reduction of dopamine receptor number. This leaves you wanting (or even needing) more, and more, and more to get even less of an effect. And the decidedly modern phenomenon impacting our dopamine more than anything else? Chronic stress.
4.
Killing Jiminy: Stress, Fear, and Cortisol
Stress is inevitable. Suffering is not. Your body is built for withstanding acute stresses. Those stresses can be physical (a car accident), adversarial (a lion or a linebacker), medical (high fever), or mental (an English test or forgetting your anniversary). Your body has a protective response to stress, designed to help you fight or flee. It will maintain your blood glucose so that you don’t pass out, protect your blood pressure so that you don’t go into shock, and prevent inflammation. All of these are mediated by the release of the hormone cortisol from your adrenal glands, which sit on top of your kidneys. You need cortisol, perhaps more than any other hormone, in order to survive; without it, the very thought of getting out of bed is an abomination.
Acute, short-term cortisol release is both necessary for survival and is actually good for you. It increases vigilance, improves memory and immune function, and redirects blood flow to fuel the muscles, heart, and brain.1 Your body is designed for cortisol to be released in any given stressful situation, but in small doses and in short bursts. Today, even though our acute stresses are declining in frequency and severity (most of us are far less likely to be chased by a lion in our daily lives), our chronic stresses are going through the roof. Despite (or maybe because of) electricity, computers, cars, indoor climate control, and food everywhere, the prevalence and severity of chronic psychological stress and its attendant cortisol effect is taking its toll.2 I’ll lay 20 to 1 odds it’s the same for you.
Stressed to the Max
Long-term exposure to large doses of cortisol will kill you . . . but slowly. When pressures are relentless, your cortisol response can remain elevated for days, months, or years. Evidence of the associations between job stress, psychological distress, elevated cortisol, depression, and disease is extremely compelling. Psychological stress in adolescence is directly linked to the risk
of heart attack3 and diabetes4 in adulthood. Chronic stress also directly impacts the reward pathway as described in Chapter 3, and it has been shown that chronic stress can speed the onset of dementia.5
The Whitehall study looked at the health of twenty-nine thousand British civil servants over the course of thirty years. Those lowest on the socioeconomic scale had the highest rates of chronic disease and also of cortisol levels.6 Even after controlling for behavior (e.g., smoking), death rates were directly related to high stress and the multiple pressures of being financially insecure. Like our friends across the pond, middle- and lower-class Americans also suffer from the highest rates of diabetes, stroke, and heart disease. And if you’re not Caucasian, the stresses associated with racism only exacerbate these effects. There are certainly genetic influences, but the fact is that African-Americans and Latinos tend to suffer from higher rates of morbidity from almost every disease than their white counterparts, and stress plays a huge role in this dichotomy.7, 8
Whatever the mechanism, stress breeds more cortisol. And the more stress, the more breakdown of the endocannabinoid CB1 receptor agonist and anti-anxiety compound anandamide, and the more anxiety.9 This is where marijuana comes in—to curb the anxiety of everyday living (depending on what you got your marijuana prescription for). Like other drugs, marijuana acts on a specific part of the brain and, depending on whether you are a person who gets paranoid from a few tokes, it can, like, seriously, help you to mellow out. However, chronic marijuana users show long-term cognitive decline to the tune of 8 IQ points,10 so, in the end, they may be less stressed about reality anyway.
A Bucket of Nerves
The release of cortisol and your body’s reaction to stress are the result of a cascade of responses. Threat is first interpreted in a walnut-sized area of the brain called the amygdala (see Chapter 2). Whether it’s evading a lion or a line of creditors, your amygdala is scanning the environment for these threats, and talking with other areas of the brain to determine how you should handle it. How your amygdala interacts with the rest of the brain in response to stress determines how you respond, be it curling into a ball or chillaxing. Stress is inevitable. It’s your amygdala scanning the scene and how it connects with your other emotions that determines whether you will be safe or sorry. If you don’t tame your amygdala early, it can become a devastating creature (see amygdala-taming classes online and Chapter 18).
When a threat is detected by the amygdala, several things occur. First, the amygdala activates the sympathetic nervous system (SNS). The SNS raises blood sugar and blood pressure, to prepare you for the acute stress. Second, like the childhood game of telephone, the amygdala tells the Hypothalamus (the brain area that controls hormones), which tells the Pituitary, which tells the Adrenal glands to release cortisol, known as the HPA axis (like the Gossip Girls). But long-term, this can exact a toll on your arteries and your heart, leading to hypertension and stroke. Third, the amygdala is normally in reciprocal communication with the hippocampus, which is the memory center of the brain. The hippocampus is the set of the Pixar movie Inside Out (2015), where memory “bubbles,” colored by associated emotions, are stored. The amygdala and hippocampus are supposed to check and balance and exert feedback on each other.
When all is working well, the acute stress you experience is transduced into memories in the hippocampus so that you don’t put yourself in the same situation again (a “disgust”-colored memory bubble reminds you that too much tequila leads to an unpleasant morning). Or you are able to realize that, just like last night, the scratching at the door is not a burglar but rather the dog wanting to go out to do his business. Of all the parts of the brain, the hippocampus just might be the most vulnerable to cell death. Almost any brain insult you can imagine (low blood glucose, energy deprivation or starvation, radiation) can knock off the neurons of the hippocampus. And one of the serial killers that attacks the neurons in the hippocampus is cortisol. The longer your cortisol stays elevated, the smaller and more vulnerable your hippocampus gets, which puts you at risk for depression.11 This is likely why chronic stress is associated with memory loss12 and why the mothers of toddlers find their car keys in the refrigerator (and not because the kid put them in there).
Executive Function Dysfunction
Excess and chronic stress impacts your ability to reason. The prefrontal cortex (PFC) is your “high order” or “executive function” conscious part of the brain (see Chapter 2). Each of us has our own personal Jiminy Cricket, like the character from Pinocchio, which keeps us from indulging in bad behavior and keeps our baser desires in check. In an uncontrollable stressful situation, the amygdala–HPA axis commands the release of neurotransmitters including dopamine (yup, that again).13 These flood the PFC, silencing Jiminy, which disinhibits you from doing some wild and crazy things.14 When your PFC is under fire by cortisol, your rational decision-making ability is toast. You can’t differentiate between immediate or delayed gratification.15 So, instead of your Jiminy telling you to “Zen” when someone steals your parking space, you are much more likely to react on impulse and extract your short-lived justice, just as Kathy Bates’s character in the film Fried Green Tomatoes (1991) did (Towanda!).
Worse yet, the more cortisol the amygdala is exposed to, the less it is dampened down by—you got it—the law of mass action. More cortisol means fewer cortisol receptors in the amygdala, and the more likely your amygdala will do the talking from here on.16 Chronic stress day by day weakens your inner Jiminy17 to the point where the amygdala becomes your outer Cricket. You just react to the slightest provocation without any thought of consequences.
So the amygdala is responsible for your reaction to stress and the release of cortisol. It also interacts with the VTA, the site of the dopamine neurons. Stress and cortisol also shift your bell-shaped dopamine curve to the right (see Chapter 3), thereby increasing reward-seeking behaviors. Increased stress can turn a small desire into a big dopamine drive,18 which can be quenched by either drugs or food, or both. This is how the pizza and beer scenario typifies the American food experience.
Experiments in animals emphasize that either stress or corticosterone (the rat version of cortisol) administration increases the drive to consume various drugs of abuse, such as cocaine.19 One way to drive up the stress of rats or monkeys is to house them in groups. Invariably one monkey, through wits, guile, or brute force, will become the alpha male and have the power to maintain social control over the others, especially in regard to food and breeding. The alpha’s cortisol levels are lower than any other member in the social group. When provided access to cocaine for self-administration, those on the lowest end of the pecking order are the ones that become the addicts.20, 21 America’s middle and lower classes suffer from more chronic stress than the rest of the population: not knowing if there will be sufficient money to pay the rent, working two or more jobs, facing mountains of credit card debt, food insecurity, and a general sense of powerlessness—all ramp up your cortisol. One can argue that this population is at higher risk not only for obesity, heart disease, and stroke22 but also for drug use and addiction.23
Faulty Brakes
Stress-induced dopamine release also has the capacity to remodel the PFC, so now Jiminy isn’t even a Cricket anymore; he’s been squashed like a bug.24 These neurons (the ones that house the dopamine receptors) are fewer and farther between.25 And, if you bombard them enough, you kill them off and they don’t grow back (see Chapter 5). You need even more to get less. By driving the stimulation of the amygdala and decreasing your cognitive control centers, stress and cortisol make it much more likely that you will succumb to temptations. Three deep breaths or three doughnuts? Depends on the office you work in.
When cognitive control is lost, the ability to inhibit the drive to seek pleasure is lost. Stress promotes faster addiction to drugs of abuse26 and is likely the reason why drug addicts find it so impossible to quit. Chronic stress kills off neurons in the PFC, which is a pred
ictor of addicts relapsing.27 Why do you think rehab centers are generally in scenic areas and designed to be low-stress? It’s upon leaving treatment, when addicts are confronted with the stresses of the real world, that some will start using again. This occurs with food as well.28 Obese people have been shown to have a thinning of their PFCs, likely secondary to long-term dopamine and chronic cortisol bombardment.29
And what is America’s preferred drug of choice in dealing with stress? The one that is closest at hand. And that would be—you guessed it—sugar. Both animals and humans increase their food intake when stressed or when experiencing negative emotions, regardless of whether or not they are hungry. The boss is yelling at you? Krispy Kreme seems as good a solution as any. And there’s actually a reason for this. High-energy dense food, aka comfort food (think chocolate cake)30 increases acute energy to the brain and thus reduces the amygdala’s output and subsequent stress.31 Stress may affect food intake in several ways. For instance, people with eating disorders tend to show higher levels of cortisol or greater cortisol reactivity.32
Alternatively, if stress becomes chronic, and eating is the preferred coping behavior of the individual, then highly palatable food, especially food laced with added sugar, may also become addictive. Cortisol is an appetite stimulant; infusion of cortisol into humans rapidly increases food intake.33 Those who put out more cortisol in response to chronic stress also consume the most comfort food in response to stress.34 It gets worse. Cortisol actually kills neurons that help to inhibit food intake. Thus the stress and reward systems are linked, with food (usually sugar) being the drug,35 breeding a new generation of stress eaters.36 Break out the Ben & Jerry’s.
The Hacking of the American Mind Page 6