High Price

by Carl Hart

  The green blips on the oscilloscope were coming fast and furious. Poppoppoppoppop was the sound accompanying the images, which were generated by the firing of neurons in a region of the rat brain called the nucleus accumbens. I was monitoring the experiment, studying the effects of morphine or nicotine on these brain cells. Previously, I’d operated on the rat, delicately implanting electrodes into the accumbens to measure the way the neurons there would react to the drugs. Although we couldn’t tell directly using this technique, we believed we were studying cells that used dopamine as their neurotransmitter, since these were the most common type of cell in that brain area.

  It was 1990. I was an eager young college student, working at the University of North Carolina Wilmington. President George H. W. Bush had labeled that year as the start of the decade of the brain. Dopamine was at the center of addiction research. Researchers like Roy Wise and George Koob had propounded the theory that all psychoactive drugs that people enjoy—everything from alcohol to cocaine to heroin—increased the activity of dopamine neurons in this region.1 This was believed to cause intense pleasure, which in turn produced desire for more.

  And, in the case of drug use, that desire was said to be so overwhelming as to “hijack” the brain’s “pleasure center,” a major part of which is known as the nucleus accumbens. According to the theory, this center was supposed to be activated by “natural” rewards like sex or food, things that would help an animal compete in the evolutionary race for survival. But drugs can increase the activity of dopamine neurons even more than these ordinary pleasures. As a result, with their brains taken hostage by these unnatural experiences, addicts were seen as inevitably doomed to lose control over their behavior. The need to chase more dopamine would leave them begging, borrowing, stealing, dealing, even killing for more drugs as a result. Dopamine was said to make crack cocaine irresistible and crack addicts’ behavior uncontrollable.

  This “dopamine hypothesis of addiction” had its beginnings in an accidental observation by James Olds and Peter Milner at McGill University, in Montreal, way back in the early 1950s. They had heard in a lecture that a brain network then known as the reticular activating system (RAS) would motivate rats to learn mazes better if it was stimulated electrically. Increasing the activity of the cells in this network appeared to make rats more alert and more successful at remembering the maze. Eager to study this for themselves, Olds and Milner placed electrodes into rat brains (similarly to the way I would later do, though I was measuring activity rather than adding electricity to stimulate the brains of my rats). They tried to place the electrodes so they could stimulate the RAS.

  Once these electrodes were implanted and the rats had recovered from the surgery, the researchers placed the animals, one at a time, in a box. Each corner was labeled: A, B, C, D. Whenever the rat wandered over to corner A, the scientists hit a button to electrically stimulate its brain. Most of the rats just wandered aimlessly. But one particular rat would repeatedly return to corner A, especially during the stimulation, as though the stimulation had made this corner very attractive.

  Olds and Milner began to wonder if they’d misplaced the electrode in this rat. They decided to examine its brain closely to see where the probe had landed. When the researchers dissected its brain, they found that they had indeed put the electrode in the wrong spot, accidentally landing in a region known as the medial forebrain bundle (MFB).

  Initially, the researchers thought they’d discovered that the MFB made rats curious or interested. And that was probably part of what was going on. But in order to try to figure out exactly what was happening, they next deliberately implanted electrodes in this region in other rats. Instead of stimulating their brains manually, however, Olds and Milner put levers in the rats’ cages to allow them to stimulate themselves. And, once the scientists let the rodents start pressing the lever, some began hitting it up to seven hundred times an hour.2

  Though these findings have been exaggerated—in both the scientific literature and popular press—to make it look like no rat could ever “just say no” to this type of self-stimulation, many rats actually didn’t learn to self-stimulate and couldn’t be trained to do it. As with drug addiction, this is not a phenomenon that can be understood in isolation from the rest of the environment, even in rats. And as with drug addiction, the truly compulsive behavior was seen only under specific conditions.

  Nonetheless, Olds and Milner soon realized that they might be on to something much bigger than a way to enhance learning. They’d discovered some kind of joy spot—in fact, the area soon became known as the brain’s “reward” or “pleasure” center. Later, in the 1960s, other researchers would discover that the most abundant neurotransmitter in this region was dopamine and that the MFB carried signals between regions we now think are involved in pleasure and desire, such as the nucleus accumbens.

  The rats’ behavior with the lever appeared to be a model for reward that could be used to study addiction. Now all that was left to do, it seemed, was to figure out how different drugs interact with dopamine and then discover ways to block this. Addiction might be cured, once and for all.

  Over time, however, as you’ve probably guessed by now, it’s a lot more complicated than we initially thought. When dopamine’s prominent role in reward was proposed, there were only about six known neurotransmitters: dopamine, norepinephrine, serotonin, acetylcholine, glutamate, and GABA. Now there are more than a hundred. Furthermore, we now know that there are specific receptors—or specialized structures that recognize and respond to a particular neurotransmitter—for each neurotransmitter, and most neurotransmitters have more than one type of receptor. For example, dopamine has at least five receptor subtypes—D1–D5. We also now know that hormones like oxytocin and testosterone can act as neurotransmitters.

  But despite these ever-intensifying complexities, our theory about dopamine’s role in reward has not been appreciably revised since it was originally proposed. And, as you will see later, a growing body of evidence casts doubt on this simplistic view of reward.

  Nonetheless, when I started studying addiction, I was a true believer in the dopamine hypothesis. I thought that dopamine probably drove sexual and gustatory excess, that it made crack cocaine addicts crazed with cravings. Many of the researchers I worked with were convinced; my heroes were people like Olds and Milner and Wise and Koob, who had made key discoveries through animal research on brain mechanisms involved in reward. I thought that if we could just understand how drugs of abuse interacted with this neurotransmitter, we’d easily develop better treatments—perhaps even a cure—for addiction. The answers were in this one chemical in this key circuitry of the brain.

  Soon, however, certain research findings began to make me skeptical of this idea. These included some of my own. For example, my master’s research involved studying how dopamine was removed from the pleasure-linked nucleus accumbens after nicotine was administered. At the time, some researchers were claiming that cocaine and nicotine acted similarly on dopamine in this area, even though data also suggested that rats pressed levers far more times and would work much harder for cocaine than they would to get nicotine.

  Indeed, trying to get rats to press levers for nicotine was one of the most difficult experiments I ever tried. I didn’t succeed and I’m not alone. Plenty of researchers also failed at this task. (Incidentally, trying to get rats to press for THC, the active ingredient in marijuana, is even more difficult.)

  In my master’s work, I looked at how nicotine affected dopamine’s action in the nucleus accumbens. But what I was seeing was unexpected: nicotine wasn’t acting at all like cocaine. Some of the behavioral effects might be similar in some situations, but in this brain region, the two drugs actually had opposite effects.

  The oscilloscope that I monitored displayed a line representing how quickly the dopamine activity rose or fell after a drug or saline solution was given. And those lines looked very different when you compared what happened with cocaine to what
was seen with nicotine. With nicotine, the line would go up and then fall off more quickly than with saline.3 But with cocaine, it would go up and stay up much longer than with saline.4

  This meant that nicotine was increasing the rate at which this brain region “mopped up” dopamine—in other words, nicotine was taking dopamine out of the connection between brain cells (the synapse) where it has its effect, faster than would occur naturally. But cocaine was acting in the opposite way. It was keeping dopamine active in the synapse for longer.

  Because this finding contradicted the conventional wisdom and threw a bit of a monkey wrench into the neat story that was being told about dopamine and drugs, there was some resistance to it at first. Charlie Ksir, my PhD preceptor, and I published the first two papers detailing this research in 1995 and 1996. Some researchers did not want to believe that we were correct. Antismoking activists didn’t like it, either, because it got in the way of the useful rhetorical claim that cocaine acted similarly to nicotine in the brain, which claim had allowed them to amplify arguments about nicotine addiction by implying that it was just like the nefarious crack.

  Soon, however, our findings were replicated and expanded on by other researchers.5 Years later, in fact, I was approached by tobacco companies, whom I turned down on more than one occasion. They, of course, wanted to enlist me in their efforts to stress the differences between their drug and cocaine. The distinction that we found, however, didn’t mean that nicotine wasn’t addictive or even that it wasn’t ultimately increasing dopamine’s activity.

  But it was one clue that the dopamine story wasn’t as simple as it first appeared. Although both nicotine and cocaine eventually have the effect of increasing dopamine activity in the brain, they do this via quite different mechanisms. Cocaine delays the termination of dopamine’s actions, while nicotine causes neurons to release more dopamine in the synapse. Moreover, each drug also has differential actions on a range of other neurotransmitters, all of which actions can result in very different subjective experiences. Smoking cigarettes and smoking cocaine don’t feel identical to most people, after all.

  And there were further complications. Researchers began to find that dopamine was released not just in pleasant situations; such releases also occurred during stressful or aversive experiences that were not at all enjoyable. For example, some studies show that dopamine levels rise when animals are stressed by electric shocks or cues that predict painful or negative experiences. Moreover, while animals stop self-administering drugs like cocaine if dopamine is blocked, the same isn’t true for heroin.6 If dopamine were the only brain source of pleasure, heroin administration—indeed, administration of any pleasurable drug—should also cease.

  In addition, drugs that release dopamine, such as amphetamine (Adderall), methamphetamine (Desoxyn), and methylphenidate (Ritalin), are used therapeutically, not just on the street. These medications are often prescribed for attention deficit/hyperactivity disorder (ADHD), both in adults and in children. They’re also utilized for treating obesity and narcolepsy.

  But although there are some cases of abuse, the vast majority of therapeutic users do not become addicted. Indeed, there’s some evidence that children given these drugs to treat attention problems are actually at lower risk of addiction later in life than those whose ADHD is not treated with medication.7 These drugs always cause increased dopamine release: if elevated dopamine-related pleasure alone produces addiction, why don’t these patients become addicts, always driven to get more?

  The problem is that when we study things like addiction, we’re focusing on pathological behavior and ignoring what occurs under the most common, normal conditions. In reality, most drug use doesn’t result in addiction. Very little research has been reported about drug users who haven’t lost control over their behavior or animals who won’t press levers for nicotine or THC. Even less is understood about the activity of the brain’s reward system when people engage in the most naturally rewarding behavior of all: sex. We don’t know much about how sexual behavior is encoded in the brain and regulated, and it’s hard to tell what’s wrong with a brain system when you don’t know what happens when it works properly.

  For me, even in my teenage years, when I was certainly as driven by sex as any adolescent male, it wasn’t something that controlled me. I wanted it, for sure, and I was certainly proud of my reputation as a player. But staying in control was paramount. That was far more important to me than any particular girl or experience of sex. In fact, I remember going to basketball practice one day, immediately after having sex with Monica, the girl with whom I’d earlier had that embarrassing first orgasm. I’d been out all night—and was definitely tired when I hit the court. My friend Jimmy Lopez, who was a guard on a rival team, was watching.

  “Damn you moving slow; that pussy must’ve gotten to you,” he said. I was horrified by the idea that he might gain confidence and think that he could dominate me on the court. So I never did that again. After that, I’d abstain before games like a boxer: I didn’t want to take the chance that sex could make me less agile. I certainly liked sex and spent a great deal of time chasing it but I always stayed in control.

  Also, like most of my friends, I wouldn’t deign to fight over a girl. We saw that as uncool; it meant that you cared too much. A player didn’t act impulsively out of jealousy. He couldn’t be seen as dependent on any one woman’s love. Of course, you’d step up if someone insulted your lady or disrespected you by flirting with her in front of you, but that was about your own status on the street, not about her. Desire, compulsion, and control had to be more complicated. It just seemed impossible that this one neurotransmitter, dopamine—one found in only about 1 percent of all brain cells—could, by itself, produce uncontrollable behavior when its levels rose and you felt good.

  CHAPTER 5

  Rap and Rewards

  Social support helps to lessen the negative consequences of stress.

  —ELIZABETH GOULD

  The cavernous indoor basketball court at Washington Park Gym was almost unrecognizable at night. The slippery concretelike floor, which I’d cursed as I’d played on it with the City Park team because it was so hard on the knees, almost seemed to thump along with the bass line. The crowd moved in pulsing rhythm, the girls all dressed in their tightest Jordache, Sassoon, or Gloria Vanderbilt jeans, with belly-skimming tops that highlighted their curves. Lights flashed across the packed-in bodies, revealing different scenes and groups as the colors changed. I’d never seen a party like it before—nor had I ever wanted more to be a part of something.

  At the center of it all were the DJs, controlling the sound from behind a wooden Formica-covered stand. One of them was dating my sister Brenda. He would eventually become her husband and they are still married to this day. Brenda met Kenneth Bowe when I was in seventh grade. It was Kenneth, his brothers, and some of my other sisters’ boyfriends who would become the closest thing I had in my life to an active father. These men got me into deejaying, at which I soon aspired to shine with the same competitive spirit I brought to athletics. During our weekly dances, they also schooled me on how to be a man.

  Brenda had Kenneth take me along to my first dance when I was eleven or twelve. As in much of my social world, the crowd was exclusively black. There were no bleachers at Washington Park Gym, just a regulation basketball court surrounded by open space that could hold several thousand people. When the party started, it seemed like the center of the universe.

  I remember the excitement, the scintillating energy, the pounding bass, the sheer joy of being in a crowd merged in music and amped up by surging teenage hormones. That first night, I was tentative because it was all so new to me. In fact, that was one of the only times I ever danced in public, trying not to look like a fool and moving with the crowd. That was before I knew that the cool people were on the DJ platform or behind the booth, just hanging.

  Dancing wasn’t cool if you had a better way to strut your stuff, like making the scene itself by playi
ng the music or being involved with the guys who did. I felt insecure and unsure initially, but I soon sized up the situation, recognized where everyone ranked in the social hierarchy, and figured out where I wanted to be.

  Before I hit high school, I mainly just watched from behind the DJ stand. Observing Kenneth’s brother Richard, who was probably the top DJ in all of South Florida then, I learned how to mix and spin, how to work the mic, and the basic mechanics of operating all the sound equipment. We had Technics turntables and QSC amplifiers. JBL and Electro-Voice speakers provided that booming Miami bass. There were enough electronics to fill a room in Kenneth’s mother’s house, with literally thousands of records squeezed into his shelves.

  Soon I could hear what flowed, what kept the party rocking, and how to blend one beat seamlessly into another. From Richard—who went by the DJ name Silky Slim—I learned how to build the crowd up and feed into its growing energy. I could tell what beats were slamming, when to play a slow jam, and how to bring an evening to a climax, to build bumping backbeat onto bumping backbeat until it seemed like the room itself would explode.

  Early on, of course, I didn’t get much play: the older guys would let me spin a few songs and say a few words, just to see if I could do it. I was still a little kid to them. But when I showed that I was more than a cute novelty, that I was really able to move the crowd, I began to get longer sets, and by the time I was fourteen, I was part of the group itself.

  Deejaying at a dance circa 1983.