The Pleasure Instinct: Why We Crave Adventure, Chocolate, Pheromones, and Music - Gene Wallenstein (2008)
Part III. The Pleasure Instinct and the Modern Experience
Chapter 11. Homo Addictus
Every form of addiction is bad, no matter whether the narcotic be alcohol or morphine or idealism.
—Carl Jung, 1963
Vices are sometimes only virtues carried to excess!
—Charles Dickens, 1848
Most people have no idea how much their brain changes on a daily basis.As you read these words, distinct neural ensembles are communicating with one another, shuttling electrical impulses across brain space. In the process some of these neural paths become strengthened and others are weakened. This collective pattern of brain activity creates a map or neural representation of the information being learned. As we have seen in previous chapters, some things are generally easy to learn if they are related to an organism’s overall fitness or survival. Information not directly related to important selection factors may be more difficult to learn if it has little or no fitness relevance. The degree of difficulty in learning something is generally measured by seeing how long it takes to master the new information. For instance, if you become nauseous after eating dinner at a particular restaurant, you do not need additional meals to form the association between sickness and the local greasy pit. This is true for all mammals. Rats that are made sick by ingesting tainted food will avoid the food and location where it was consumed after a single experience. In contrast, it takes much longer to learn and remember multiplication tables or word definitions, information that—one might argue—is not directly relevant to survival or reproductive success.
As a young professor, my scientific interests focused on understanding the changes that occur in the brain as something is learned and remembered. Deep in the medial portion of your temporal lobe, there is an area called the hippocampal formation, which lights up like Carnivale as you learn new information and begin to store it into long-term memory. A great deal is now understood about the cellular and biochemical changes that occur in the hippocampus and related structures during learning and memory. Changes of this sort are generally referred to as neural plasticity, a phenomenon associated with a host of normal and abnormal conditions.
Many scientists who study neural plasticity also study addiction, since it is believed that the transition from casual substance use to dependency is accompanied by distinct changes in the way disparate brain regions communicate with one another. A number of modern treatments for addiction, as we’ll see, focus on blocking these changes in neural communication. Such phenomena can be studied readily in mice and rats, although there are obvious limitations in making the conceptual leap from animal models of addiction to understanding the disease process in humans. My approach to help bridge this gap was to volunteer at a local adolescent facility for substance abuse to hear about the addiction process from people who have experienced it firsthand.
The building in which I was eventually to spend so many afternoons was an old converted Victorian house on the outskirts of downtown. I learned quickly that the treatment model at this facility was holistic. Kids aged twelve to seventeen years resided in the house for therapeutic periods ranging from roughly three to twelve months. A typical day included meals, four hours of school, individual and group therapy, medical appointments with physicians and psychiatrists, meetings with legal counselors if required, and family visits. Kids came from all over the West and for a variety of reasons. Some had been in trouble with gangs and been arrested repeatedly. Others were at the house for behavioral problems at school or home. A common theme among the kids was substance abuse that could involve alcohol and/or controlled substances, including prescription medicines.
From the beginning, I was deeply moved by the emotional stories I heard from the residents. Several common topics came up again and again, including childhood traumas such as physical, sexual, and verbal abuse. Other kids were impacted severely by a single early event such as the death of a parent or sibling. After several months I began to see patterns in an individual’s choice of drugs that seemed to map onto the particular circumstances that surrounded his or her life.
Alberto was a seventeen-year-old boy who had been repeatedly plucked off the streets of Phoenix by authorities for crimes related to gang activity. When I first met him, he didn’t seem violent, but I knew Alberto had been arrested at least once for assault on a rival gang member. He wasn’t a terribly big guy and, to me, he seemed almost easygoing. If anything, he projected a sense of detachment bordering on apathy.
Each resident participated in group sessions three times a week. A session typically began with each resident giving a brief update on his or her current state and bringing up any problems to the group. Alberto never seemed to have any problems. Like many new kids, he seemed to think of group therapy as a chore that was best done as quickly as possible or avoided entirely. After the update period, the group would focus on one person and explore the circumstances that brought them to the house. During his first turn Alberto seemed painfully uncomfortable. He appeared unable to focus and became more and more frustrated with each passing minute. The group, however, had seen this before and gave him time. Gradually he began to tell his story.
Alberto came to the United States from Mexico when he was eight years old. He and his mother moved into a small, two-bedroom apartment with other family members, including his aunt and uncle and their four children. He described his uncle as a chronic alcoholic with a quick temper who physically abused him and his cousins fairly regularly. Alberto attended school for a couple of years when he first immigrated to the States, but dropped out and got more involved in gang life in his early teens. By the time he was thirteen years old, Alberto had tried almost every drug available on the street and was selling methamphetamine with a crew of other kids and a connection out of Los Angeles that could be traced back to Mexico. His favorite drugs were methamphetamine and cocaine, both of which he consumed regularly.
One summer night, after a day of meth binging, he had a psychotic episode. He described the experience as a waking dream in which he heard angry voices yelling at him, but he could not understand exactly what was being said. He also felt worms crawling under his skin, and he picked violently at his arms, neck, and face until they bled. At some point in the night Alberto had a grand mal seizure and was raced to a local emergency room.The ER visit was followed by police custody. After several similar experiences, arrests, and detoxifications, Alberto was sent to our little house for full-time residential care.
The withdrawal state that he felt was fairly typical of cocaine and methamphetamine use: low arousal and a general sense of malaise. Almost all methamphetamine or cocaine users appear lethargic and extremely apathetic following detoxification. In contrast, Alberto described the feeling of a meth-induced high as being like a bull—strong enough to take on anything or anybody. It also gave him enough energy to keep him awake for days on end.The best part for him was often the anticipated high and then the feeling that nothing could go wrong once the drug took effect. In the year that I worked at the house, I saw many ex-gang members. Almost all of them were addicted to methamphetamine and described a sense of invincibility while on the drug that made it particularly attractive given the toughness of gang life.
Although the most common addiction in the house was to methamphetamine, there were also a number of residents addicted to heroin or morphine. Those addicted to heroin or morphine often had noticeably different life circumstances surrounding their drug use compared to those using methamphetamine.
Christine was a petite blonde who could easily be mistaken for the class valedictorian. She was often described by her peers as “bubbly,” instantly likable, and very smart. She came to the house from Las Vegas after running from three other rehabilitation programs. Her guardian hoped that bringing her out of state away from friends to a residential program might prove more effective in addressing her heroin addiction. I first met Christine in a group therapy session. Based on appearance alone, most people would have never guessed that she was a heroin addict. Nor would they likely be able to fathom the strange world in which she was immersed while using the drug.
Contrary to many of the kids at the house, Christine actually embraced the program and was eager to participate. In group sessions we began to learn about her surprising past. She was born just outside San Francisco, but moved with relatives to Las Vegas after her parents were killed in an automobile accident. In Vegas Christine often felt like an interloper, living with her grandmother and ailing grandfather. Shortly after arriving, her grandfather died and her grandmother sank into a deep depression. Christine was thirteen when her grandmother committed suicide, leaving her to fend for herself. She dropped out of school and lived on the street with a small group of other homeless teenagers. Her new life consisted of prostitution and just trying to stay alive. One day a friend showed up with several small vials of pure morphine stolen from a local hospital and asked if she’d like to join her. Christine had tried other drugs by then, including pot, methamphetamine, and a host of prescription drugs. She described her first morphine use as a turning point in her life. She had never had a high like this before and felt an instantaneous warmth come over her entire body—almost as if a security blanket was being tucked around her by her long-lost parents. She felt safe and, for the first time in as far back as she could recollect, less anxious and sad about her life. Before morphine, she constantly worried about everything; now all that was gone.
Christine quickly made the jump from morphine to heroin and started to get involved in petty theft, mostly stealing jewelry and wallets from hotel rooms on the less glamorous side of town. After her second arrest she was sent to a juvenile detention program that was followed by her first rehabilitation program. She was arrested a third time for prostitution less than three weeks after completing the initial rehab.
In group sessions, Christine described her gravitation toward heroin use as a logical choice, almost as if she were a pharmacist matching a treatment to a particular ailment. Her problem, of course, was extreme anxiety. The typical uppers such as speed, methamphetamine, and cocaine always seemed to worsen this state. Christine learned through her own trial and error that morphine, heroin, and sex were all ways to ameliorate this anxiety and unrest.This process was not altogether different from the experiences of Alberto, who learned that methamphetamine often made him feel more confident and brave in gang-related circumstances that can easily be described as perilous. Time and again I heard similar descriptions of how a resident came to focus on a particular drug or combination. It was not long before my understanding of addiction at the neural level started to align with what I was hearing from these kids, who had lived the experiences. The stories I heard mapped well onto theories about how different brain structures sensitive to addictive substances modulate the pleasure instinct.
At present, there are at least three major theories of addiction, each involving biological and psychological components.We will discuss these in a bit, but before we do, it may be instructive to first think about addiction as a process that interacts with emotional systems—both biological and psychological in nature.
Researchers have often found it useful to separate emotions into two basic processes, one that represents the valence of the state (positive or negative) and another that describes the level of physical arousal (high arousal or low arousal). In this two-dimensional model, one can have positive feelings involving high arousal. This state occurs when the arrival of some positive event (for example, a loved one or the smell of a tasty cheeseburger) triggers pleasurable feelings. Contrasting this, the arrival of a negative event (for example, bad news or the immediate threat of physical harm) can induce a feeling of dread or anxiety.
It’s important to remember that in this model, pleasurable feelings can also be elicited in the low-arousal state by the removal of a previous threat. Likewise, the removal or loss of a potentially useful event can lead to negative emotions. Psychologists like this model because it aligns well with experimental findings. For instance, the pleasure associated with the introduction of a positive stimulus is typically accompanied by relative increases in clinical indicators of arousal (for example, blood pressure and cortisol levels). Likewise, pleasure elicited by the removal of a constant threat (or negative stimulus) is usually associated with relative decreases in these same clinical indicators. In each case we have the same emotional end point, but an asymmetry in how one arrives at the destination.
Neuroscientists who study emotions from an evolutionary perspective also like this two-dimensional model since it corresponds well with the idea that emotions are important for identifying fitness indicators in one’s environment. An example of this is the high positive correlation between an individual’s facial symmetry and his or her perceived attractiveness by others (see chapter 9). Our world is full of fitness indicators that range from those that can be used to determine the ripeness of fruit to others that allow us to choose a suitable mate. This simple two-dimensional model of emotions extends naturally to the traditional view that hedonic states evolved as internal measurement devices for assessing fitness (see chapter 9). In this view, a given stimulus carries emotional value only if it can serve (indirectly or directly) as a fitness indicator.You might argue that this is a drastically oversimplified view of emotions, and I would agree. We will use it here only to introduce a perspective for understanding how the pleasure instinct relates to the initial attraction and subsequent abuse of drugs and other potentially addictive phenomena.
In this two-dimensional fitness model, pleasurable feelings occur with the presence of fitness benefits or with the absence of fitness decrements. Negative feelings occur with the presence of fitness decrements or with the absence of fitness increments.This model, although simple, is consistent with a large body of experimental findings in humans, nonhuman primates, and mammals.
We all know, however, that a fitness indicator that is useful at one point in historical time may not be useful at another time if the environment in which natural selection takes place changes dramatically. For example, in earlier chapters we learned that our intrinsic fondness for sweets in the forms of fructose and lactose serves an important function of feeding the metabolic machinery of each cell in our body. This fondness, which was forged by selection pressures in our prehistoric hunter-gatherer days, has turned into a pathological condition in modern environments with the advent of refined sugars. It now contributes to a number of modern health problems, including obesity, diabetes, and heart disease, to name just a few.
While this particular example makes sense, one might ask how this general process extends to a fondness for drugs or alcohol. Lactose and fructose were clearly available in our hunter-gatherer days, so it was at least possible that they might be used as selection factors. Those who could identify and consume these resources stood a better chance at surviving to reproductive age. But were alcohol and other psychoactive compounds available? Certainly we can’t expect the synthetic forms we have today to have existed during hunter-gatherer times, but what about their precursors? If such substances did not exist during ancestral times, they never could have been used as selection factors, and hence an evolutionary theory of addiction based on the hedonic model would not make much sense.
People often think psychoactive drugs are modern phenomena; they are not. They are a modern problem, to be sure, but their precursors have coevolved with hominoids through the millennia. Many anthropologists have pointed out that Homo sapiens have enjoyed a coevolutionary relationship with psychotropic plants for millions of years. In this coevolutionary arms race, mammals have evolved mechanisms to metabolize certain plant substances, and at the same time, plants have evolved toxins that mimic the chemical structure of many endogenous neurotransmitters and neuropeptides. For instance,Areca catechu, commonly known as betel nut, was being used at least thirteen thousand to fifteen thousand years ago in ancient Timor. You have probably never heard of betel nut, but it is currently the fourth most commonly used drug on the planet following nicotine, ethanol, and caffeine.There is also evidence that nicotine was being extracted from pituri plants by indigenous Australians in Queensland some forty thousand years ago.
An open question concerns how and when these substances were used. For many psychoactive substances, there is archaeological evidence that they were used in ceremonial contexts, but there is also evidence that they were simply everyday food sources and used for medicinal purposes. Our relationship with alcohol probably goes back even farther than the drugs just mentioned. Virtually every species that ingests fermenting fruit is subject to low levels of ethanol exposure. Indeed, the anthropoid diet has been predominantly frugivorous (fruit-eating) for some forty million years, suggesting that ethanol exposure is old and prevalent in our prehistory. Temperate-zone fruit sources have been shown to manifest ethanol concentrations ranging from 0 to 12 percent. Comparative studies have found that as most temperate fruit ripen, both their ethanol and natural sugar contents increase. Consequently, mammals that were consistently able to identify and consume fruits enjoyed the fitness benefits of fructose, but also ingested low levels of ethanol as part of their diet. Some anthropologists have suggested that ethanol plumes may have even been used by early mammals to identify fermenting fruit, making the identification of environmental ethanol a fitness indicator. Regardless of their use, hominids have clearly had a long relationship with plant-derived psychoactive compounds.
At this point we know three very important things. First, psychoactive substances were likely consumed quite commonly in ancestral environments. Second, mammals have evolved distinct mechanisms for detecting and consuming these substances. Third, these substances may have had fitness value in the form of medicines, food supplements, or a means to find either of the two. Hence our simple two-dimensional hedonic fitness model of emotions may apply to these psychoactive compounds. So how do emotions play a role in addiction? In particular, why does the pleasure instinct nudge some of us toward addiction, but not all of us?
The Many Faces of Vice
It is quite popular to experiment with potentially addictive drugs. More than 60 percent of Americans have tried an illicit substance at least once in their lifetime, and if alcohol is included, the number rises to more than 90 percent. But, of course, only a very small percentage of people who actually try a potentially addictive drug become addicted. For instance, recent studies have found that even for a highly addictive drug such as cocaine, only 15 percent of users become addicted within the first ten years of use. The addiction literature often focuses so intently on the particular psychological and biological mechanisms that might be responsible for the addictive process that we seldom ask the simple question as to why so relatively few users ever become addicted. An evolutionary perspective may prove particularly useful in addressing this question, since it assumes that we are all susceptible to addiction, not just some of us. Another question that can be addressed from an evolutionary view concerns why there are so many different forms of addiction. Are there psychological or biological mechanisms that are common roots for all forms of addiction, whether the compulsion is to use heroin, eat fried food, or gamble?
What are the different kinds of addiction? The answer changes depending on whom you ask. Certainly there are the classics that we all typically think of when we talk about chemical addictions such as drugs and alcohol. But what about other activities, such as food, sex, video games, surfing the Internet, thrill-seeking, shopping, and so forth, that may share common points with the more traditional forms? Let us look at the leading theories of what addiction is and how it forms.This will provide greater context for understanding how the pleasure instinct may contribute to the casual use of certain substances and how this use may transition to full-blown addiction.
There is an enormous literature in this area, but three major theories have stood the test of time. Each tries to explain the psychological variables and processes that govern the transition from casual to compulsive substance use. They are: (1) the classic hedonic view that drugs are taken for the pleasure they provide the user and that unpleasant withdrawal symptoms are the primary cause of addiction; (2) the aberrant learning perspective, which holds that addiction results from the formation of pathological stimulus-response associations; and (3) the loss of inhibitory control theory, which suggests that the brain systems that usually regulate impulsivity may be impaired, resulting in greater susceptibility to substances that provide immediate gratification. I will introduce and contrast these theories with a fourth, the modified or modern hedonic view, based on recent findings that the neural systems responsible for “wanting” a drug are different from the systems that control “liking” a drug.
The classic hedonic explanation for addiction dates to the 1940s, but it wasn’t until the work of Richard Solomon and his colleagues in the 1970s that formal theories were first developed and tested. The basic idea is that we take drugs because they bring us pleasure. Repeated exposure to the same drug, however, leads to tolerance such that ever-increasing doses are needed to get the same high. The same homeostatic neural mechanisms that lead to tolerance result in withdrawal symptoms if the drug is discontinued. Hence compulsive drug use (addiction) is maintained to avoid the unpleasant withdrawal symptoms.
The central mechanism in this theory is homeostatic in nature. There are hundreds of examples of compensatory responses that operate in living systems. All mammals live most comfortably within a specific optimal range of values for variables such as core body temperature, blood composition, blood pressure, and others. Brain cells, for example, are very temperature-sensitive. Their electrophysiological responsiveness to stimulation changes dramatically with even small deviations from a core body temperature of 37 degrees Celsius.
Cells in the hypothalamus are sensitive to temperature deviations and send feedback signals into the peripheral nervous system to make compensatory adjustments to the rest of your body that are designed to bring body temperature back into the optimal range. If you’re a member of the Polar Bear Club and just finishing a brisk winter swim in Lake Michigan, as you leave the water your hypothalamus will scream at your autonomic nervous system to make adjustments. It will send signals whose end results are to make you shiver (in an attempt to warm the muscles), develop goose bumps (to fluff your nonexistent fur), and turn your skin blue (a result of blood moving away from cold surface tissues to warm the inner sensitive core of the body).
If, on the other hand, you are involved in strenuous exercise on a very warm day, the hypothalamus activates systems to dissipate heat such as perspiration (which cools the skin by evaporation) and increasing blood flow to the skin surface, where heat can be radiated away (and make your face appear flushed). There are many other examples of homeostatic control by the hypothalamus and other brain regions, including the regulation of blood oxygen, volume, salinity, acidity, and so forth.
Ingestion of a drug that binds with brain receptors does the same thing as environmental changes do in the examples given above. It causes a shift in normal neurotransmission that will, in turn, elicit compensatory mechanisms that attempt to bring the system back to some rough homeostatic or allostatic level. But the compensatory response actually competes with the drug-induced response. This process results in users needing to increase their dosage to get the same effect.This is known as drug tolerance.When drug ingestion is stopped, the compensatory response is still active, so there is a net shift toward effects in the opposite direction of those induced by the drug. These effects operate at a number of levels and comprise the symptoms associated with withdrawal. Thus at the sensory level, the pleasure induced by drug ingestion is combated by unpleasant opposing processes that are left unchecked during the withdrawal state.
Although the classic hedonic model is appealing for a number of reasons, experimental and observational findings suggest that it is limited in accounting for several aspects of the addictive process. One problem with the theory is that it fails to explain why individuals addicted to drugs often relapse into use even after they are free of withdrawal symptoms.The compensatory response that underlies withdrawal decays over time, and therefore the supposed prime reason for continued use no longer exists. Another major problem for the theory is that many addictive substances are not terribly pleasant at first, yet they still drive compulsive behaviors. If there is no hedonic value from the start, why would use continue beyond the first neutral or even negative experience? A typical example of this effect is first-time cigarette use, which most people find very unpleasant.
Aberrant learning theory is probably the newest perspective on addiction. The basic idea is grounded in associative learning theory (see chapter 3), where a stimulus and a response become paired. Experiments in rodents have shown that distinct parts of the brain become activated when an animal is rewarded with an addictive drug (for example, the nucleus accumbens, a collection of neurons in the forebrain) and often in anticipation (for example, the medial prefrontal cortex) of the reward.There are endogenous brain receptors for all psychoactive compounds. For instance, mu receptors are activated by morphine and heroin, and dopamine receptors are activated by cocaine and amphetamines.We, of course, do not have these agents circulating naturally through our bodies, but there are endogenous analogues that have evolved as neurotransmitters and neuropeptides.There are a number of ways one can measure the affinity or strength with which a natural neurotransmitter can activate a receptor and trigger the ensuing biochemical process. The aberrant learning theory posits that modern addictive drugs have much greater potency in activating endogenous receptors than their natural counterparts and hence act like an abnormally powerful stimulus. A neural system that is designed to learn stimulus-response pairings will be hyperactivated by such a powerful stimulus, and this learning might be very quick and enduring. The theory suggests, then, that the neural systems that typically regulate positive emotions such as pleasure are fooled by an abnormally powerful stimulus (a pure drug rather than the less potent endogenous counterpart) that essentially hijacks this normal process and creates a false fitness indicator signal.
One limitation of the aberrant learning theory is that there has never been a reasonable explanation as to why an unusually strong stimulus-response association would immutably lead to compulsive behaviors. Since it is still a relatively new perspective, more studies are needed to fill in some of the missing pieces that connect alterations at the neural level to ultimate changes in psychological functioning and behavior.
The third major theoretical perspective on addiction involves the loss of inhibitory control. This perspective is really a much broader theory about the origins of impulsive behaviors and extends well beyond addiction. The famous story of Phineas Gage, a man whose life changed in the blink of an eye, illustrates how damage to the brain areas that control impulsivity affects many behaviors that are also altered by addiction.
The year is 1848, and like much of New England, Vermont is slowly stirring from its sleepy agrarian pace toward industrialization. Part of this transformation resides in the construction of several railways that will soon connect the major cities of the region. As one follows the planned route of the Rutland and Burlington line from Bellows Falls northward, the township of Duttonsville emerges within just a few miles, and we find ourselves abruptly shifting direction, moving on a westward path toward Proctorsville. It is in this small town that we find Phineas P. Gage, a foreman contracted to lay ties for this segment of our new railway.
Gage is a great favorite with the men in his gang of navigators or navvies, a term left over from the early days when many of the laborers working on the railway found prior employment in the construction of canals used for transporting goods. The men revere him because he is a diligent worker possessing an iron frame and is scrupulously fair in the way he treats those in his employ. He does not play favorites, but rather allots tasks and pay in an equitable manner.This exacting and decisive nature also makes Phineas a favorite with his employers, who consider him “the most efficient and capable man” they have.
Indeed, everyone seems to like Phineas Gage. Friends and neighbors describe him as quiet and respectful of others, and such “temperate habits” are the hallmark of a good foreman. Bosses who fail to live up to these standards are unpopular, and within the culture of violence that persists among the rail workers at present, run the risk of being attacked and possibly killed. Indeed, by the time Gage is at work on the line, several foremen have already been fatally wounded by those in their charge in and around the Cavendish area.
At the moment, Phineas and his gang are laying a portion of the track that smacks snug up against the Black River.They will have to blast away large outcroppings of rock so the line can assume a level and straight flow. Blasting involves several stages that must be performed carefully and in the correct sequence. After a small diameter hole is drilled, a safety fuse is knotted and placed into the hole. Then an explosive powder, usually made from a mixture of sulfur, charcoal, and a nitrate such as saltpeter, is placed over the fuse. Finally, sand or clay is poured over the powder and compacted with a tamping iron. The purpose of tamping is to consolidate the explosive force to as small an area as possible, thereby allowing the charge to detonate into the rock with greater efficiency rather than escaping ineffectually back out the hole.
Phineas is an old hand at this and has had his tamping iron forged by a local blacksmith to his own specifications—“to please the fancy of the owner,” others would later say. It is 3 feet, 7 inches long, 1¼ inches in diameter at the larger end, and tapered to a sharp point of ¼-inch diameter at the other end. It is quite hefty, in all weighing almost 13½ pounds.
The gang has been at work all day along a bend in the bank of the river, and Phineas has just poured explosive powder into a shallow hole about three feet deep. While waiting for his assistant to pour sand over the mixture before he tamps the charge, a commotion among the men erupts just a few feet behind him. Looking over his right shoulder, he turns to see that all is okay but must feel every ounce of the full weight of the tamping iron in his hand, for it has been a long day and it is 4:30 P.M., almost quitting time. As he returns his attention to tamp the charge, a shattering explosion occurs, and his iron, sharp side forward, is thrust up, piercing his left cheek. The projectile is moving with such extreme force that it penetrates the base of his skull, plowing through the front portion of his brain, and exits out the top of his head. Phineas immediately falls back to the ground, while his tamping iron, covered in blood, has rocketed an additional hundred yards before returning to earth. Amazingly he is still conscious and begins to speak to those stunned workers gathering around him.
Gage manages to stand awkwardly and “walks a few rods”—fifty feet or so—to an ox cart, where he rests against the foreboard and is driven the three-quarters of a mile back to his room in town. The cart lurches west past the intersection of Depot and Main streets, and when it arrives at the tavern of Mr. Joseph Adams, owner and solicitor, Phineas walks to the back, allowing two of his men to help him down. He then gently moves a short distance up three stairs and comes to rest in a small chair on the tavern’s veranda to await medical attention. It is not until some two weeks later that Phineas emerges from his semiconscious state and begins to stir.
As improbable as the accident and recovery were, and as delighted in his progress as his physicians could be, Gage’s friends soon began to realize that something in Phineas was amiss—“Gage is no longer Gage,” several remarked. Within six weeks of the accident, much of the temperament of the young foreman working on the Rutland and Burlington Railroad has now changed.Those things that made Phineas who he was, at least to his friends and family, seem to have been stripped away with the shearing force of the tamping iron. Rather than being described as one who “possessed a well-balanced mind … looked upon by those who knew him as a shrewd, smart businessman, [and] … persistent in executing all his plans of operation,” we find a new set of postaccident adjectives used to describe his character.
After recovering his physical strength, Phineas pleaded for his old job as foreman but was turned away. His contractors, who considered him the most efficient and capable man in their employ before the accident, regarded the change in his personality and behavior as so severe that they could not grant him his position again. In a letter to the Massachusetts Medical Society, Gage’s physician, Dr. John Harlow, writes, “the equilibrium or balance, so to speak, between his intellectual faculties and animal propensities, seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times perniciously obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual capacity and manifestations, he has the animal passions of a strong man.”
The description of the new Phineas as childlike was common among his friends, family, and even his physician. Gone was the man who routinely managed a large gang of navvies with competence and an efficiency that was the envy of other foremen. In his place we find a mercurial man who has no patience for plans or goals, little emotional attachment to previous friends, and seems to have lost the ability to anticipate the future and control his impulsive desire to live only in the present.
We now understand that the tamping iron damaged a large portion of Phineas’s frontal cortex, an area that we know from experiments in animals and humans is intimately involved in higher cognitive functions, including the ability to balance present needs with longer-term consequences. Rats that have very restricted damage to key neural pathways that link brain areas involved in positive emotions such as the nucleus accumbens with the prefrontal cortex have impaired learning on a number of tasks. For instance, in one study paradigm rats are given a sweetened treat, but it is accompanied by a mild foot shock. Normal rats typically learn within one or two trials to avoid the treat (even though they would normally consume it readily) and the subsequent foot shock. Rats with damage to this inhibitory pathway, however, go back again and again for the treat despite the repeated foot shock that clearly causes them distress.
There is emerging evidence that chronic exposure to some addictive drugs such as amphetamines and cocaine can reduce neural activation in the frontocortical systems that seem to regulate inhibitory control. Consistent with these findings, addicts often exhibit a very similar pattern of deficits on neuropsychological tests to those observed in patients with damage to frontocortical systems. Taken together, this suggests that individuals who have weakened frontocortical systems may be less able to regulate impulsivity, and this limitation may contribute, in part, to drug-using behaviors.
The loss of inhibitory control and its associated behavioral problems seem to be robust phenomena in certain individuals, particularly those with obvious brain damage. It is still very unclear, however, if it is possible that more subtle deficits (perhaps not involving structural damage) in frontocortical functioning would predispose an individual to drug-seeking. It is very likely that a loss of inhibitory control is just one component of the addictive process and may work alongside other mechanisms to drive both drug-seeking and compulsive drug use.
The fourth major theory of addiction is the modern hedonic perspective. This view is rooted in fairly recent findings from a handful of neuroscientists who have shown that there seem to be different neural systems that regulate the “wanting” of a drug versus the “liking” of a drug. Kent Berridge and Terry Robinson, working at the University of Michigan, developed what is more formally called the “incentive sensitization” theory of addiction. In a series of elegant experiments, the researchers delineated two neural systems that contribute to the addictive process in fundamentally different ways.
Experiments in Berridge’s lab and those of others have shown that in rats, addictive drugs alter the nucleus accumbens and related brain circuits that regulate motivational behaviors. If these circuits are lesioned in rats, the animals no longer display normal motivational behaviors such as seeking natural rewards (for example, sex, food, and water). Chemical activation of this circuitry when it is intact facilitates these motivational behaviors.This circuitry is part of the larger mesolimbic dopamine system that involves projections from brainstem regions to a number of pleasure centers such as the nucleus accumbens, larger striatum, and portions of the frontal cortex (see chapter 3).
For years, scientists thought this was the only brain system involved in reward, but we now know that at least four major systems are responsible for what we colloquially refer to as pleasure. Recent experiments have suggested that the mesolimbic dopamine system is primarily responsible for regulating motivational behaviors that make us “want” things. For instance, genetic manipulations that create mice with hyperactivated mesolimbic dopamine systems result in animals that are more motivated to obtain rewards and less distracted in reaching this goal than normal everyday mice. A major point, however, is that these animals do not display an enhanced “liking” of the reward once it is obtained—they don’t consume any more than normal mice once they actually have the reward.The incentive sensitization theory holds that repeated use of addictive drugs enduringly alters this brain circuit, which in turn makes the drugs more desirable, resulting in a positive feedback loop. The process is analogous to activation of skin histamine receptors that causes us to scratch, thereby leading to further histamine release.
The mesolimbic dopamine system is only part of the hedonic story. The other major component is the brain’s opioid system. Injection of chemicals that boost opioid neurotransmission in the basal forebrain markedly increases the actual consumption of palatable foods in rats. Moreover, opioid drugs given to humans and rodents increase their hedonic reactions to sucrose. Working in Berridge’s laboratory, Susana Pecina has identified several “hedonic hot spots” in rats that when activated by opioid agonists enhance their natural pleasurable response to sucrose. Likewise, blocking opioid neurotransmission at these sites decreases the hedonic response or “liking” of sucrose.
These findings address a key limitation of the traditional hedonic model, namely, why people become addicted to an initially unpleasant experience (such as smoking or ingesting alcohol for some individuals). Indeed, many people who are addicted report that the pleasurable feelings initially felt when first using the drug subsided over time with continued use, yet they still felt strongly compelled to use the drug—they still wanted it, even though they did not necessarily like it. The fact that there are two entirely different neural systems that mediate distinct components of the pleasure instinct helps explain why many times there seems to be a dissociation between wanting a drug and liking a drug.
These components may have very different dynamics during the different states of drug use. Initial drug use, for instance, is most likely mediated by both mesolimbic dopamine circuits and the opioid system (that is, both wanting and liking). The transition to compulsive drug abuse may, in turn, be mediated primarily by the mesolimbic system, since many addicts complain that they do not experience the same hedonic response or “liking” once addicted as they initially did from the drug. One can further imagine that overactivation of the mesolimbic dopamine system, coupled with disruption to frontocortical inhibitory circuitry that may occur with amphetamine and cocaine use, could result in a particularly dangerous combination where drug wanting is enhanced and inhibitory control is reduced.
Berridge’s lab has recently discovered that yet another brain system may help regulate “liking.” The cannabinoid system (see chapter 6) overlaps in many locations with the opioid system. For instance, both have connections in the nucleus accumbens, but, of course, utilize different chemical neurotransmitters. Microinjection of the cannabinoid agonist anandamide into the nucleus accumbens of rats enhances their liking responses to sucrose in the same way as do opioids. Further work is now being done in multiple laboratories to determine how broad the cannabinoid circuitry is and to what extent it overlaps with the other two transmitter systems involved in the pleasure instinct.
Each of these three systems is known to have wide networks that stretch across the entire brain. In addition to the forebrain locations mentioned above, each of the neurotransmitter systems has brainstem sites that seem to play a similar role in the wanting or the liking component of the pleasure instinct. Indeed, a fourth neurotransmitter system may involve benzodiazepine/GABA.Work in the late 1980s demonstrated that when decerebrate animals that have had their brain-stem transected from the rest of the brain were injected with a benzodiazepine drug (which enhances GABAergic neurotransmission), it enhanced their liking reactions to sweet tastes.
Hence there may be four distinct neurotransmitter systems that mediate the pleasure instinct, each with brain-stem origins.The fact that there could be so many brain-stem locations for inducing different components of the pleasure instinct is interesting and expected since, as we have seen in earlier chapters, these areas are the first brain regions to develop during gestation. Indeed, proper functioning of brain-stem areas is critical, since they control so many fundamental processes that support living organisms (for example, respiration, sleep-wake cycles, feeding, thermal regulation, and so forth). These are ancient brain regions, conserved across all mammalian species. Evolution has built upon their foundation. The central theory espoused in this book is that these brain-stem sites are responsible, in part, for using pleasure to nudge developing humans toward certain stimuli that must be experienced for normal brain development to continue. We have described this process as a kind of neural bootstrapping where activation of key brain regions induces pleasure when the right kinds of stimuli are experienced. The processing of these stimuli is required to stimulate the development of “higher” brain areas. Such a mechanism is dependent on the ability to activate the pleasure instinct at a number of brain regions as the developmental process unfolds.
The pleasure instinct is regulated by several major brain systems that originate in the brain-stem and project to higher levels of the brain. Each system may support different components of the initiation, sensorial processing, and perceptual feeling of pleasure during normal functioning. This pleasure circuitry coevolved with potentially addictive substances in the forms of plant and fruit compounds, but we have no way of knowing whether such substances led to addictive behaviors in early Homo sapiens. It is clear, however, that the refinement of certain compounds into more potent forms has led to their pursuit via the pleasure instinct on a pathological scale. The jump from fructose and lactose to refined table sugar is one example. The invention of distilled alcohol and synthetic compounds are two more.These agents mimic endogenous neurotransmitters that activate systems that normally use the pleasure instinct as a common metric for evaluating fitness.A key problem with modern compounds (especially those that are synthetic) is that they have tremendous potential for overactivating these circuits, since they are not metabolized in the same manner as their naturally occurring counterparts.
Although the modern hedonic theory of addiction has addressed some limitations of the earlier hedonic model, there are still many open questions about how addiction occurs and what can be done therapeutically to intervene early. The perspective advanced here does shed some light on several issues. First, it provides a biologically based mechanism, consistent with evolutionary theory, for understanding why we are all susceptible to drug and alcohol abuse. The same neural mechanisms that promote normal brain development through birth and well into the adolescent years drive us toward certain stimuli that signal high fitness value.This biological imperative translated into improved odds for surviving to reproductive age in ancestral environments. Clearly, however, this process can lead us toward some stimuli and experiences that may have adverse consequences in our modern environment.
The theory suggests, then, that each of us—not just the few with an unlucky genetic disposition—is susceptible to addiction. From this perspective, it is not so surprising that many people become addicted to these substances. Indeed, it is perhaps most surprising that only a relatively small percentage of people who experience drugs actually become addicted. Of course, a great deal of variation exists from individual to individual in how these neural systems communicate with one another, and some of this is undoubtedly modulated by genetic influences. Much of the evidence discussed above indicates that these systems are also readily modulated by environmental experiences, including drug use, stress, and a host of other life circumstances.
Even a casual observer would note the persistent relationship between chronic stress and drug use. Chronic stress and the associated activation of the body’s response (for example, increased cortisol, adrenocorticotropin hormone, and corticotropin-releasing factor) have severe and deleterious effects on the neural systems that regulate emotions, including the pleasure instinct. Often these neural changes accumulate slowly, but they can last long after the stress has been reduced or even eliminated. For instance, in a landmark study, ethologist Dee Higley and colleagues showed that adult rhesus monkeys that were stressed for six months immediately after birth by being removed from their mothers exhibited increased stress responses (measured both physiologically and behaviorally) when compared to littermates who were allowed parental attachment during this critical period. Interestingly, the adult monkeys who were stressed at birth exhibited increased ethanol consumption under free-range conditions when compared to normally reared littermates. Monkeys that were not permitted to form a social attachment with their mothers during this critical developmental period grew up to be adults that exhibited greater fear and startle responses and increased physiological markers of stress (for example, cortisol production), and were more likely to consume a mind-altering substance than those that were able to establish a maternal bond during this period.
This is consistent with my experiences at the residential treatment house. Perhaps the most intriguing part of working at this facility was that the kids seemed to use drugs that elicited specific portions of the pleasure circuitry that compensated for the type of stress they were experiencing. Alberto, like many gang members, used methamphetamines to activate his mesolimbic and associated neural systems, giving him a sense of high energy, confidence, and strength, all requirements to combat the stress that accompanied gang life. Christine, on the other hand, gravitated toward increased sex and heroin use, which strongly activated her opioid system, eliciting a sense of calm and serenity—feelings that compensated for the abrupt loss of social attachment to her parents and grandparents. When adequate social bonds failed to develop (signaling a fitness decrement), Christine showed a tendency to engage the neural systems that promote feelings of attachment and calm through natural (via increased sex) and pharmacological means.
Understanding how the pleasure instinct may contribute to drug-seeking, drug use, and addiction is important, since the theory has implications for treatment. For instance, much of the literature examining the biology of addiction has concentrated on the mesolimbic dopamine system. Drug use can alter this system in a number of ways, including (1) decreases in dopamine-containing cell size in the basal forebrain; (2) enduring increases in postsynaptic dopamine receptor sensitivity; (3) alterations in the release of dopamine from presynaptic sites; and (4) a cascade of intracellular changes that occur, which ultimately impact dopamine transmission. Each of these presents a possible therapeutic target for combating drug-seeking and addiction on the “wanting” side. However, our theory predicts that agents that downregulate dopamine transmission may also have anti-hedonic effects, perhaps making them less tolerable to patients.
When we consider experiences like those of Alberto and Christine, and add what is now understood about the different neural systems involved in the pleasure instinct, it is probably safe to conclude that not all drugs induce the same hedonic experience. Another potential therapeutic target might be the opioid system, using compounds such as oxytocin agonists and prolactin agonists, which have been shown to reduce separation distress in animal models. Clonidine, an alpha-1 noradrenergic agonist, has been shown to reduce separation distress in rats and is already being used effectively in clinical practice to amerliorate opioid withdrawal.
Clearly, far better than treating an addiction already in progress is to implement ways to limit the likelihood of people feeling disenfranchised from family and society in the first place. There is accumulating data showing strong relationships among disruptions in normal social dynamics, drug use, and abuse.There is also a growing scientific literature demonstrating that both drug use and social bonding engage common pleasure circuitry. Providing additional social support structures, particularly for adolescents, might help reduce the likelihood of engaging these circuits through drugs and alcohol if they are experiencing social problems.
Finally, it should be said that the pleasure instinct offers but a single perspective on addiction. Certainly, no one theory explains all of addiction. Given what we now know about the disparate brain systems that different drugs engage, it is highly unlikely that there will ever be a single cure that fits all. However, as basic biological research continues to unveil the mysteries of how emotions are modulated by brain circuits, each new discovery presents a potentially novel therapeutic target. Understanding the environmental and experiential factors that also engage these circuits might offer therapeutic avenues that are just as appealing (or perhaps even more so) as those dreamed up by pharmaceutical companies. As we will see in the remaining chapter, modern life offers us a plethora of nonpharmaceutical ways to engage the neural circuits controlling the pleasure instinct.