The Pleasure Instinct: Why We Crave Adventure, Chocolate, Pheromones, and Music (27 page)

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.