The Pleasure Instinct: Why We Crave Adventure, Chocolate, Pheromones, and Music (28 page)

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.

—Lord Byron,
Don Juan

—Ecclesiastes

 

 

 

This book began with a single question: why does pleasure exist? A passionate debate, framed on one side by hedonists and on the other by stoics, has raged since antiquity about the nature and utility of pleasure, and has influenced virtually all facets of social life in the Western world.Throughout the course of history popular opinion on the matter of pleasure—intermixed with its many political, legal, religious, and moral implications—has never found a stable resting point. Instead, it has swung back and forth like a pendulum. Conservative eras in which the pursuit of pleasure was, at least publicly, tempered have often been followed by more permissive periods, and vice versa.

Epicureans are usually thought of as representing an extreme position in this debate, one that advocates unchecked pleasure-seeking to the abandonment of all social responsibilities. Yet this is a modern distortion of Epicureanism, which originally held that happiness is attainable only if one distinguishes between pleasures that are natural and necessary, such as eating and drinking, from those that are simply desired. Ancient Epicureans followed a rather austere lifestyle, sacrificing some pleasures to avoid greater displeasures.

This philosophy laid the groundwork for the emergence of the sensualist ethics movement of the seventeenth and eighteenth centuries, a view that prevailed in the writings of thinkers such as John Locke and David Hume in England, and François Diderot in France. The central idea of this movement is that our senses are the final judge of what is positive or negative. Experiences that bring pleasure to the senses are deemed good, while those that displease are judged as bad. In this context the foundation for morality resides with the individual and is relativistic, a viewpoint that ultimately gave rise to utilitarianism in the nineteenth century.