Source: New Scientist
Date: 11 October 2003

The pleasure seekers

Hedonism makes our world go round, but it goes a lot deeper than our obsession with sex, drugs, rock 'n' roll and chocolate. Neuroscientists are completely rethinking how our brains give us pleasure, and as a result are starting to believe that the quest for pleasure may underpin every decision we make. It may even have laid the foundations of consciousness, as Helen Phillips explains.

IT WAS an outlandish, ethically questionable experiment, but this was the 1960s after all. Psychiatrist Robert Heath of Tulane University in New Orleans hoped to cure his patients' depression, intractable pain, schizophrenia, suicidal feelings, addiction, and even homosexuality - which in those days was considered a psychiatric disorder - by drowning them out with pleasure, induced by an electrode implanted deep in their brains.

Heath's experiments were based on findings from a decade earlier that administering a mild electric shock to the equivalent brain area in rats - the "reward centre" - would send the animals into a state that looked like ecstasy. The rats would work at complex tasks over and over for the promise of another shock. Heath wondered whether his human subjects would react in the same way - and they did. When they were given a shock they said they felt good. And when handed the electrode's controls, they just kept on pressing, again and again, sometimes a thousand times in succession.

Unfortunately for Heath, the good feelings waned almost as soon as the current was cut and the method did not provide any long-term benefit. Heath himself eventually moved into other lines of psychiatric research. But his experiment remained one of several that cemented the orthodoxy that creating pleasure in the brain was a simple matter of pressing the right neurochemical lever. For poets, writers and metaphysicians down the ages, pleasure had been a subtle, many-sided enigma to do with contemplating the likes of God, love or a beautiful garden. But now it seemed Nirvana could be equated with squirting a few microamps of electricity into a tiny part of the midbrain.

By the 1980s, the circuit diagram of this reward centre had been worked out. A whole series of brain areas had been charted and the chemical transmitter that passed messages around was known to be dopamine - hence the reward centre's alternative name, the "dopamine system". Everyone agreed on the centre's function, too. It rewarded animals for doing things with survival value - eating or having sex, for example. In the years that followed, the reward centre and dopamine release were linked to every natural and unnatural pleasure imaginable - everything from the cotton-wool whoosh of heroin and the wham-bam of orgasm to the gentler satisfaction of a rich meal or the thrill of winning money. And until recently that's pretty much how things still stood. The role of this brain area in addiction has also been explored in thousands of papers and studies. Millions of dollars in research grants have been spent dissecting its every neurochemical quirk. Its role is to make us feel good. It's the brain's G spot.

Except that some scientists think the issue of pleasure in the brain is far from settled. At the University of Michigan in Ann Arbor, neuroscientist Kent Berridge is carrying out experiments that just don't fit the picture. He thinks the electrodes were filling those patients and rats not with pleasure, but with a subtly different feeling - desire. Heath and other researchers, he thinks, mistook wanting for liking. Meanwhile, Edmund Rolls at the University of Oxford has been finding pleasure in a completely different brain area, the orbitofrontal cortex just behind the eyes. And Jaak Panksepp of Bowling Green State University in Ohio, Ann Kelley from the University of Wisconsin, Madison, and others are discovering that opioids, not dopamine, may be the real key to transmitting feelings of pleasure.

No one can quite agree how all the findings fit together, but they are gradually evolving into a new model of how and where pleasure is registered in the brain. The basic idea that pleasure is a reward for doing something that promotes survival remains important, but pleasure is turning out to play a much wider role. It seems to be involved in all types of decision making, from choosing food to solving mathematical problems. Pleasure helps us plan our movements and allows our brains to filter and sort the mass of smells, sights, sounds and other information that bombard our senses. It may have been the origin of all our emotions. Perhaps even consciousness itself evolved from the simple sensing of pleasure and displeasure.

At first glance, the "reward centre" idea seems hard to fault. The self-stimulation experiments, beginning with rats in the 1950s and followed by the human experiments in the 1960s, seemed perfectly clear. Modern brain-imaging studies have confirmed that the centre works overtime whenever you're enjoying something, whether it's sex or chocolate, drugs or music. And chemical analysis shows that, whatever your pleasure, dopamine fuels the circuit. "Dopamine was the pleasure transmitter," says Berridge. "The evidence seemed so strong. If you shut down dopamine signalling by giving a drug that blocks dopamine receptors, you dilute the reward value of everything." So why did he and others begin to question the status quo?

Berridge reckons that his doubts began to creep in around the late 1980s, with a few surprise results. He'd found that he could watch rats' facial expressions to judge their reactions to certain tastes. Believe it or not, rats actually look pleased when given sweet things to taste, and produce the rat equivalent of a disgusted look in response to bitterness. The assumption was that these expressions were of pleasure or displeasure, mediated by the reward centre. The surprise came when Berridge blocked the dopamine signal with drugs. In theory, with dopamine knocked out there was now no way for the rats to sense the reward value of the sweetness, so he was expecting not to see any "pleased" expressions. But the rats seemed just as expressive as ever.

Putting it down to experimental error, Berridge tried a more foolproof test. He used rats in which dopamine-producing cells had been wiped out with a neurotoxin. It was already known that these animals simply stopped eating. "They would voluntarily starve to death if the experimenter didn't intervene and feed them," says Berridge. Researchers had always thought that the rats' lack of dopamine meant they didn't like food. But when Berridge force-fed them with sweet and bitter liquids, their facial reactions were normal. "They still showed the proper positive face to sugar and the proper negative face to quinine," he says. "It looked like their reaction to pleasure was normal even though their dopamine was gone."

What was going on? The experiments prompted Berridge to look back at Heath's brain electrode results. He was struck this time by what feelings the subjects reported. They all said they felt good, and always pleaded for more when the controls were taken away. But was it pleasure? The reports mentioned feelings of alertness, warmth and goodwill, arousal, a desire to masturbate, or to drink even though they weren't thirsty. It sounded more like desire than pleasure. This fitted perfectly with Berridge's rats. Even with no activity in the reward area, they seemed to "like" the taste of sweet food. They just didn't "want" it. Could the dopamine system be a desire circuit that mediates our feelings of wanting something, rather than a pleasure centre that supplies our feelings of liking?

Although it was Berridge who drew attention to the distinction between wanting and liking, he is by no means the only researcher to realise that "pleasure" is not quite the right term to attach to activity in the dopamine system. If people are given drugs that block or stimulate dopamine release, it doesn't alter how much they report liking certain tastes. What that suggests is that the dopamine system itself doesn't produce feelings of pleasure, says Panksepp. "The dopamine system is about motivation and seeking. It gives a generalised desire or urge, an eagerness to engage with the world."

Studies of drug addiction add weight to the idea that the dopamine system is not about pleasure but desire. Addicts always end up needing more of their drug to keep the pleasure level steady. But they never say they develop a greater "liking" for any drug - they just "want" it more and more.

George Koob, a neuroscientist and addiction specialist at the Scripps Research Institute in La Jolla, California, agrees that dopamine is primarily involved in activating both movement and thought. And while he believes that its release can be directly pleasurable because it gives us a sense of power and a sense of enjoyment in "getting going", the dopamine system seems more important for helping us to make the behavioural choices that will help us achieve the goals it has told us we desire.

Pleasure chemicals

So where do we actually feel pleasure? It's not just a trivial question. According to Kelley, only by understanding the brain's pleasure and desire circuits fully are we likely to make progress in understanding two of the biggest threats to public health in the developed world, obesity and drug addiction.

One suggestion is that pleasure comes from a different group of brain chemicals. Pleasurable drugs don't just activate the dopamine system, they also trigger the release of endorphins and encephalins - a family of chemicals known as the opioids, which include drugs such as morphine and heroin. These chemicals all seem to activate a circuit deep inside the brain which overlaps with the dopamine system. Could this opioid circuit be the source of pleasure, while dopamine produces the related feeling of desire?

One clue that the opioids are involved in pleasure is their well-known effect on appetite. Even before the brain's own opioids and their targets were found, neurobiologists knew that heroin and morphine could bring on the munchies and seemed to enhance the pleasure of eating. More recently, naloxone, a chemical that blocks the action of opioids, has been found to reduce people's enjoyment of food without reducing their feelings of hunger, making things taste less pleasantly sweet, for example. What's more, Panksepp has found that young rats that are distressed by being separated from their mothers, for example, release opioids when they return, and can be calmed without their mother by opioid drugs. He concluded that social pleasures, particularly the feelings of comfort and safety associated with social bonding, are produced by opioids too. Opioids, then, seem to mediate "liking".

So where are the opioid receptors in the brain? Some are sprinkled at either end of the old reward centre, which has led many researchers to argue that opioids merely complement the action of dopamine.

More recently, however, Berridge and others, notably Kelley, have found that the opioid receptors are not confined to the dopamine system but are widespread in the brain. Berridge believes what they have found is a distinct pleasure circuit, driven by opioids. It overlaps considerably with the dopamine system, to the point where some cells take part in both circuits. But its role and chemistry are quite different.

Early results seem to show that one of the most important sites for "liking" is the ventral pallidum, a small region deep in the brain, near the dopamine system. Opioid injections into this area seem to boost enjoyment of sweet tastes, while damaging it makes all normal liking disappear - as seen by the lack of pleased facial expressions in rats given sugar. "This is a prime candidate for coding liking," says Berridge. The ventral pallidum takes in signals from the nucleus accumbens - a central component of the dopamine system - and passes them on to the cortex. He believes it could well be at the heart of our liking response.

And if this brain structure is the heart of pleasure, then a team in Oxford may have located its head. According to their research, pleasure is not created solely by deep brain structures and opioid cells. Cells nearer the surface of the brain have a vital role as well. And astonishingly, it seems that each form of pleasure is linked with a unique subset of these neurons. Some of the cells react to sweet food, others to eating fatty morsels, others to monetary reward, and so on.

The cells are all in a region of the forebrain called the orbitofrontal cortex (OFC), so-called because it lies behind the orbits of the eyes. The region has long been known to have something to do with emotions. But the Oxford team, led by neuroscientist Edmund Rolls, have now put it in the hedonistic driving seat.

Rolls points out that pleasure, like other emotions, is a direct response to a sensory stimulus. And one of the first brain regions to process sensory information is the OFC. Signals such as taste, touch, smells and sounds travel first to the sensory cortex, and from there go straight to the OFC. Visual information enters by a slightly less direct route. From here the signal passes into the opioid and dopamine circuits.

When he scanned the brains of human subjects using fMRI (functional magnetic resonance imaging), Rolls found that a nice or nasty smell, taste or touch is represented in the sensory cortex simply as a magnitude - strong brain activity for a strong smell and weak brain activity for a faint one, for example. But by the time it has passed on to the OFC the strength of the fMRI signal now correlates with how nice or nasty people rate the stimulus. As each sensory signal passes through the OFC, it is as if it becomes tinged with a level of liking or disliking.

Crucially, Rolls and his colleagues found that activity in the OFC increased or decreased in line with the level of pleasure people reported they felt after drinking, eating or sensing a touch. Even abstract pleasures such as music, attractive faces and financial reward seem to correlate with activity in this region. And each form of pleasure is linked to a unique group of neurons. Some may react to sweetness, others to fat, others to monetary reward. All told, about 10 per cent of the neurons in the OFC may be pleasure sensors.

Most pleasure sensors are probably inbuilt, Rolls suggests, encoded in our genes and honed by evolution. But the OFC can learn others. There's no innate circuit for monetary reward, he points out, but one could easily be built through learning. Money could come to be associated with food rewards or comfort, and become rewarding in its own right.

The OFC, says Rolls, also calculates when you should stop partaking in something pleasurable, through an effect he calls sensory-specific satiety. After a while any reward loses its appeal. It's not clear what causes the effect but it seems to be linked to a drop in activity in the pleasure cells. He believes drugs wreak their havoc because they tap directly into the opioid and dopamine circuits, bypassing the OFC, which might otherwise put the brakes on by exerting some kind of satiety.

The ventral pallidum and OFC are central to the new view of pleasure, but other brain regions may be involved too. A team at the university of Iowa in Iowa City has uncovered evidence that other parts of the brain's cortex become especially active during pleasure, or at least when people recall situations that gave them pleasure. Working with his colleagues Hanna Damasio, Daniel Tranel and Antoine Bechara, neuroscientist Antonio Damasio used PET scans to show that the cingulate cortex and somatosensory cortex light up in this way. Damasio thinks the observation points to a crucial distinction that must be made between pleasure as an "emotion" and pleasure as a "feeling". He sees emotions as physiological processes that guide behaviour, whereas feelings only arise when the brain experiences those physiological processes and reflects upon them.

According to Damasio's model, the emotion of pleasure may well involve the dopamine and opiate circuits and OFC. But actually feeling pleasure requires a level of reflection that can only be provided by these other brain regions. These, argues Damasio, enable us to sense how the physiological process changes the body's state. And as such they come from the parts of our brain that carry sensory maps or representations of our bodies - the cingulate cortex, somatosensory cortex and certain parts of the brainstem.

Having discovered pleasure centres all over the brain, researchers are now asking, what are they for? And the answers they are finding suggest that pleasure exerts its influence on all kinds of basic brain processes. Far from being a heady, purely human pursuit, pleasure may be a very simple and evolutionarily ancient invention.

Pleasure probably emerged for one simple purpose - to guide actions. At any one time an animal has all kinds of conflicting requirements: eat, drink, stay safe, mate, get warm. And each is producing a motivation to do something about it. "There must exist in the brain a common currency that allows motivations to talk to one another," says Michel Cabanac from the department of physiology at Laval University in Montreal, Canada. "If there was not such a currency it would be impossible to rank priorities."

Cabanac carried out a series of experiments trying to find out whether pleasure is what allows us to prioritise our actions and carry them out in the most efficient way. He compared all kinds of motivations: money, pain, comfort, palatability and so on. "In all cases pleasure was indeed the common currency that allowed the motivations to talk to one another," he says.

In one experiment, Cabanac asked people to perform a climbing task on a treadmill. The subjects had control of its speed or slope, and so could decide how to complete the task - climb fast and finish quickly, or climb more slowly for longer. The way they made the decision was based on pleasure, Cabanac says. They weighed up the discomfort in their limbs and chest with the pleasure they would gain by completing the task. The same happens when we choose what food to buy. People strike a balance between the displeasure of spending money and the pleasure of eating palatable foods. "If you combine the price with palatability you realise at each instant [people] make decisions out of the algebraic sum of hating to spend money, with loving to get good foods."

Decisions, decisions

We use pleasure to make all kinds of decisions, says Cabanac - solving a mathematical problem, forming grammatical phrases, making ethical choices, gambling. By showing people multiple-choice answers to all kinds of questions or problems and asking them to rate how much pleasure they felt reading each, he found that their ratings matched well with the answers they subsequently chose. All decisions are made to maximise pleasure, he says. We call it "gut instinct", but in reality it is seeking pleasure. His ideas are backed up by the case of Phineas Gage, a famous 19th-century patient who suffered brain damage to his frontal lobes, leaving him unable to feel any emotion. Revealingly, he was also unable to make decisions.

Clearly, though, humans are not slaves to instant gratification. We are able to override the desire for immediate pleasure. But even this decision can be viewed as one that ultimately maximises pleasure, because only by deferring gratification can we gain the chance of long-term rewards.

The fundamental role pleasure plays in decision making is leading some researchers to see it as a basic biological process that evolved long before humans did. Cabanac believes it arose somewhere between amphibians and reptiles, while Damasio thinks even flies and molluscs can have pleasure, if not the feelings associated with them. "Pleasure and pain were the earliest forms of emotion to evolve," says Panksepp. Our rich inner world of thoughts and feelings, and conscious awareness itself, may all trace back to a simple sense of pleasure and displeasure.

Unfortunately for the hedonists among us, the role that pleasure has in guiding our behaviour seems to produce a natural limit. Pleasure, by definition, cannot be long-lasting. It must switch off so that we can move on to the next task.

By similar argument, we'll never achieve true happiness through the pursuit of pleasure, says Cabanac, because we can never be truly comfortable while we are in a pleasurable state. If we're experiencing pleasure it's because we must need something. Take temperature. Only if we're too hot or cold will we be able to experience the pleasure of a cold drink or hot bath. Once our temperature has stabilised, we're indifferent to either experience. If we are in no danger or need of any kind, we're in a comfortable but indifferent state. "Pleasure - sensory pleasure - is not happiness, it is joy," says Cabanac. "The state of indifference is what I call happiness."

Helen Phillips
and further reading

BLTC Research
Musical Pleasure
Pleasure Seekers
Dopaminergic flies
The Orgasmic Brain
The Good Drug Guide
Utilitarianism On The Net
Utopian Brain Stimulation?
The Hedonistic Imperative
Electrical Brain Stimulation
Critique of Brave New World
The Neurobiology of Pleasure
Sports cars and the pleasure centres
When Is It Best To Take Crack Cocaine?
Cyborgs, Transhumans and Neuroelectronics
Pleasure Evoked by Electrical Stimulation of the Brain
Compulsive thalamic self-stimulation: a case study (1986)(pdf)