Healthy Brain, Happy Life (30 page)

TAKE-AWAYS: REWARD AREAS INVOLVED IN PLEASURE/LIKING

•  Reward includes liking (pleasure), wanting (motivation), and learning about future rewards based on past experience.

•  Early studies by Olds and Milner identified specific brain areas that rats, when given an opportunity to self-stimulate, would obsessively stimulate for hours on end. This was our first insight into the reward system.

•  The full reward circuit is a complex set of brain structures that include the ventral tegmental area, nucleus accumbens, ventral pallidum, several parts of the prefrontal cortex, cingulate cortex, and insula.

•  The key subareas of the brain associated with pleasure are a specific region of the nucleus accumbens, ventral pallidum, orbitofrontal cortex, cingulate cortex, and insula.

•  A key unanswered question is which of these brain areas or their interactions are actually causing the sensation of pleasure.

HOW ADDICTION MESSES WITH OUR BRAIN’S REWARD SYSTEM

The American Society of Addiction Medicine (ASAM) defines addiction in the following way:

Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual
pathologically
pursuing reward and/or relief by substance use and other behaviors. Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death.

We know that release of dopamine is big part of our liking and wanting response. What drugs of abuse do, at least initially, is cause a much bigger dopamine hit (estimated to be two to ten times higher) than you typically get with a natural rewarding stimulus (for example, sex or chocolate), which is what helps make these drugs so intoxicating and irresistible. Many people (myself included) feel a form of addiction to exercise and negative withdrawal symptoms when we don’t get our regular fix, but because the dopamine response is typically nowhere near as high as those from drugs of abuse, these responses don’t come close to reaching the official ASAM definition of addiction. During the first stage of addiction, called acquisition, it’s the artificially high surge of dopamine that can be the first step toward real dependency.

For example, cocaine acts directly in places where dopamine is released (such as in the nucleus accumbens) and blocks the normal reuptake of dopamine into the brain cells, resulting in a lot more dopamine floating around the brain than is usual. It’s this high concentration of dopamine in the nucleus accumbens that causes the euphoric cocaine high. The normal brain is simply not used to that big a hit of dopamine, and the feeling you get is, as a consequence, unlike anything else you have ever felt. That’s part of the reason it is so intoxicating. By contrast, heroin targets the brain’s opioid receptors, which are found all over the reward circuit, including the VTA and the nucleus accumbens. Remember, receptors are the entry gates into the cells. Activation of the opioid receptors in the VTA stimulates the release of dopamine. Nicotine has yet another way to stimulate dopamine. When you smoke a cigarette, nicotine enters the bloodstream and activates receptors in the VTA called acetylcholine receptors, which in turn stimulate the release of dopamine. In this case, the dopamine release gives smokers that hit of pleasure with every puff. While all three of these addictive drugs give pleasure in the form of a high, each one provides a different kind of feeling because they are all activating the dopamine system in different ways, in different places in the circuit, and at different levels. It’s those differences in the precise way the anatomical pathways are activated and the level of that activation that produce the different “flavors” of reward. Recent work has suggested that a major role of these drugs of abuse is to stimulate the wanting part of the reward cycle. While intense liking is certainly part of early drug acquisition, this system seems to quickly focus on the wanting part, which researchers are still trying to precisely identify.

After acquisition, escalation is the next phase of addiction, when drug use increases. One of the reasons escalation happens is because the very first hit of drug that spikes your dopamine feels amazing, just like the very first bite of ice cream on a hot summer day, but the fifth, sixth, and seventh bites don’t feel the same; the only way to reclaim the initial feeling for a drug addict is to take more of the drug, more frequently. Over time your brain becomes less and less sensitive to the dopamine, and the decreased response drives you to take more and more of the drug to try to get back to that initial maximal dopamine response.

A major factor that helps determine predisposition to addiction is your genetic makeup. It is estimated that between 40 and 60 percent of a person’s risk for addiction is genetic. You might think that people who become addicted get particularly intense levels of pleasure from the drugs, but paradoxically, they have a specific genetic modification that makes their dopamine receptors less responsive than people without that genetic modification. For people with a genetic propensity for addiction, a particular hit of dopamine (through alcohol, cocaine, sweet foods, or any other dopamine-stimulating substance) will cause less of a high than that same hit of dopamine in others. The people with a genetic predisposition for addiction will need six drinks to get to a level of intoxication that comes with two drinks for others; they need four packs of cigarettes a day, not just one.

Genetic factors contribute in yet another way to addiction factors. It turns out that drugs like cocaine affect the expression of many different genes within the nucleus accumbens, and one of those genes affected expresses a protein called DeltaFosB, which all of us have in our brain. With each injection of cocaine, you get a buildup of DeltaFosB in your nucleus accumbens cells that stays around for six to eight weeks, all the time building up more and more every time cocaine is ingested. There is evidence that the accumulation of DeltaFosB is the actual switch that activates addictive behavior. For example, just elevating levels of DeltaFosB in the nucleus accumbens alone, with no previous drug treatment, makes mice start to ingest more and more drugs relative to control mice. This is thought to be a molecular switch that keeps the addictive behavior going even when no drug is around. This is why those who have stopped abusing drugs often turn to other addictive behaviors; their neural pathways have been altered. This same protein also seems to be involved in the rewiring of the brain that occurs with long-term addiction. With long-term cocaine use, the dendrites (those branchlike input structures on neurons) in the nucleus accumbens become bigger and bushier. This in turn makes the neurons even more receptive to information from other areas, and scientists suspect that the areas that become more influential are the inputs from the hippocampus and the amygdala. This means that all the memories for the events, contexts, and emotions associated with taking drugs have an even stronger influence on the nucleus accumbens. This is thought to be the biological basis of craving: When memories of the drug-taking events get activated by the enhanced pathways and there is no dopamine around, the person experiences a craving. It’s these long-term anatomical changes to the reward circuit that make recovery from addiction so difficult and relapse so easy.

While the vast majority of us will not become cocaine or heroin addicts, a different kind of addiction hits home for many more of us. It’s called sugar. Many people feel addicted to sugar at one point or another. I felt it when I went through my Twix candy bar phase when I was training with Carrie (see Chapter 4). Like most things that bring us pleasure, sugar also activates the same reward circuitry as cocaine and heroin, albeit to a lesser degree. However, in one disturbing recent study researchers showed that rats given the choice between intensely sweet liquid and cocaine actually chose access to the intensely sweet liquid more than even high doses of cocaine, showing that in some situations, the sugar and sweet taste can be more rewarding than even cocaine. The scientists hypothesized that this striking effect may be due to the fact that mammals (including both rodents and humans) evolved in an environment low in sugar and, therefore, we may be hypersensitive to high concentrations of sugars. They hypothesize that exposure to lots of sweets, as is common in the modern world, might cause a hypersensitivity of the reward system to sugars, causing the response they saw in their rats. It’s clear that an addiction to sugar is at least part of the problem in people with eating disorders, and scientists are starting to realize that sugar addiction can have serious consequences. We are still trying to understand the addictive qualities of sugar, how it relates to drugs of abuse, and how to cure that addiction when it happens. There are still no answers, but one promising avenue of research is the effects of exercise to curb addictive behaviors.

CAN EXERCISE CURB ADDICTION?

Some drug rehab centers are already strong believers in the power of exercise to treat addiction. For example, the Odyssey House, a New York City–based facility for treating addiction, runs a highly regarded program that trains recovering addicts to run marathons. It’s called the Run for Your Life program and was started by Odyssey House executive vice president, chief operating officer, and former drug addict himself John Tavolacci. Tavolacci credited marathon running with helping him beat his drug addiction. Odyssey House residents joke that before they sign up for the Run for Your Life program, the only running they did was away from the police. The program helps residents start slowly, with short but regular training runs through Central Park. They gradually build up to longer and longer runs, culminating in their ultimate event: the New York City Marathon. Talk about a runner’s high! The Odyssey House believes in the power of exercise to help treat addiction. But what’s the neuroscience behind this idea? The neuroscience is based on the interaction of exercise with the same reward system that drugs of addiction interfere with, and there is promising evidence that exercise intervenes at several key stages of addiction and becomes a replacement behavior.

First, strong evidence shows that adolescents involved in team sports or who exercise regularly are less likely than physically inactive teens to use cigarettes and illicit drugs. While these findings are suggestive, they don’t prove that physical exercise actually causes the decreased drug use, they suggest only a correlation. However, research in animals does provide causal evidence that exercise decreases the chances of developing an addiction. In these studies, rats given the choice between a running wheel and the ability to self-administer methamphetamine will administer fewer drugs than the rats without the access to the running wheel. Similar results were found for alcohol. This suggests the very exciting idea that exercise can work as an effective substitute for drugs. While this level of exercise in rodents (or sports participation in high school students) clearly does not produce the same dopamine burst as the drugs themselves, it seems that it does produce enough of a dopamine buzz to compete with the drug consumption. While we know a lot about how exercise can work to decrease initiation of drug taking in rodents, more studies are needed in humans that directly examine the effects of exercise intervention programs on decreasing drug use. But progress is slow because the studies are both difficult and costly.

Another key phase of addiction that may be the most challenging is withdrawal from drug use. It is so challenging because it has been reported that up to 70 percent of recovering addicts relapse to drug use within one year after treatment. This is a period during which craving and depression can drive people back to drugs. The good news is that there is strong evidence in humans that exercise can have beneficial effects on withdrawal symptoms, particularly in smokers. Exercise has been shown to decrease cigarette cravings, withdrawal symptoms, and negative affect. The bad news is that nicotine is the only drug of abuse that has been studied thus far.