How chemical manipulation can undo the Pavlovian responses that dog human nature

July 6, 2001

What links addiction, gambling, bungee-jumping and Parkinson's disease? Geoff Watts reports

The brain chemical dopamine, a neurotransmitter or chemical messenger, is best known for its role in Parkinson's disease. Make too little of it and you will develop the tremor, slowness of movement and other symptoms of this debilitating illness. But to imagine that this is the only reason to take an interest in dopamine is to underplay its importance to the brain.

For example, people with Parkinson's are disproportionately likely to be non-smokers - not only following the emergence of their illness, but before it. There are two possible explanations: that smoking protects against Parkinson's; or that some subtle differences in patients' brains make them less susceptible to the pleasure of a cigarette. When you learn that patients are also less likely to develop any other form of addiction, the latter explanation becomes the more appealing. This conclusion is reinforced by studies that show links between the cause of Parkinson's, obsessive behaviours such as gambling or video-game playing and even aspects of personality. Common to all these is the brain's output of dopamine and changes in this output and the response to it, brought on by disease or other events.

Alain Dagher, of the Montreal Neurological Institute, specialises in imaging the brains of people with Parkinson's. "Because it's caused by dopamine deficiency in the basal ganglia," he says, "people originally thought that this region of the brain must be involved in controlling movement, especially its accuracy. In fact the role of the basal ganglia is probably in learning new movements or skills. Things like playing the piano."

You acquire a skill of this kind by repetition. Work in animals has shown that normally functioning basal ganglia are important in motivation and reward. Rats, for example, need the basal ganglia to learn to find food in a maze. And the main chemical messenger in this motivational system is dopamine.

"This is where drug addiction comes in," Dagher says. "In the normal animal or human, dopamine is released in rewarding situations. For a human this might be when you've just played the piano well and feel a sense of achievement. Dopamine acts as a sort of teaching chemical. It tells you that the movements or behaviours you've just completed were good in some way."

This is how drugs of addiction might work. Taking almost any drug causes a release of dopamine in the brain. The behaviour - drug taking - is rewarded and so reinforced. A process that is positive when associated with learning a new skill is destructive when linked to drug use.

One of the obstacles facing the addict who wants to give up is conditioning. Nearly all drug-taking is ritualised and closely associated with specific actions and places.

Many ex-smokers feel an urge to light up when entering a pub; heroin addicts who have kicked the habit are more likely to succumb when visiting the scene of their drug-taking days. These Pavlovian responses have also been shown, especially in animal studies, to be associated with the dopamine system.

Psychologist Gavin Phillips, of York University, has been investigating the role of dopamine in conditioning - and the possible therapeutic value of chemicals that affect dopamine production. Psychological methods of overcoming conditioning depend on breaking the link by putting addicts in circumstances that trigger their craving but then denying them access to drugs. If this behavioural remedy could be supplemented by a chemical manipulation of the dopamine system, the combined effect might be more powerful.

Phillips is encouraged but cautious about this way of undoing Pavlovian associations. "There are different kinds of dopamine receptor in different parts of the brain. You'd want a compound to be very specific. Otherwise you might have something like the side-effects of the older anti-schizophrenic drugs which upset systems that were totally irrelevant to the illness."

Trevor Robbins, of the department of experimental psychology at Cambridge, has spent many years researching the dopamine system. Like Phillips, he is sure that manipulating it will eventually contribute to overcoming addiction, but stresses that to rely solely on pharmacology would be a mistake.

Alain Dagher and researchers at London's Hammersmith Hospital have used scanning techniques to study the release of dopamine in the brain. The group hit on the idea of stimulating the system by having their subjects play video games. "We found that dopamine was produced while they played," he says. "And their performance was correlated with the amount released."

It would be highly speculative to say that this is why video games are "addictive", he says. But he believes that there is an element of truth in the idea.

He also suspects that much the same applies to gambling and to obsessive compulsive disorders.

Which brings us finally to personality. "There's good evidence that part of your personality is inherited, and that one aspect of this relates to dopamine genes," Dagher says.

"People who score high on novelty-seeking - bungee-jumping and so on - have a higher rate of addiction than those who score low. We know that novel experiences bring about a release of dopamine, and that there's also a correlation between the density of dopamine receptors in the brain and your personality type."

From Parkinson's to personality, the dopamine system is a key player in a tangled web of brain functions. How much that key will eventually unlock is still unknown.

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