Impulsive minds are primed for drug addiction

Impulsive rats are improving our understanding of human drug addiction. Because of differences in the way their brains process dopamine, these animals are predisposed to addiction, even before they’ve touched a drug.

We’ve all acted impulsively before, and we have the horrendous clothes, echoing bank accounts and hilarious memories to show for it. But science is beginning to show that impulsive people may be particularly vulnerable to drug addiction, and there is little funny or harmless about that.

Millions of people around the world are addicted to drugs like nicotine, cocaine, heroin and alcohol.According to Government statistics, half a million people in the UK are addicted to class A drugs like cocaine, heroin and amphetamines.

All too often, drug addiction and other compulsive disorders like obesity are dismissed as issues of ‘willpower’ and those who succumb to temptation are labelled as ‘weak’.

But this attitude is at best wrong, and at worst stigmatising and self-righteous. And it provides no clues for ways of helping people with these problems.

In fact, the evidence suggests that drug addiction is linked to certain personality traits. Being impulsive is possibly one of them, and being keen to seek out new sensations (often described as “living life to the full”) is another.

But do these traits drive people towards drug addiction, or are they a result of the drugs themselves?

Some scientists have suggested that long-term drug use impairs our prefrontal cortex, a part of our brain that helps to suppress our basic urges, and is essential for appropriate social behaviour. It’s the mental equivalent of the angel on our shoulders. By relieving us of this restraining effect, drug use could lead to impulsive, reckless and anti-social behaviour.

Impulsive people are more likely to become addicted to drugs like cocaine.But a new animal study suggests that it works the other way round too. Innate differences in personality traits can predispose individuals to addictive drugs, even before a single molecule has entered their system.

Jeffrey Dalley, Trevor Robbins and colleagues at the University of Cambridge studied a dozen rats, who were cocaine virgins at the start of the experiment. The rats were trained to associate a light with the arrival of food; when it came on, the animals received food if they waited and pressed a button.

Some of the rats were twice as likely to prematurely press the button than others, allowing Dalley to separate them into an ‘impulsive’ and a ‘non-impulsive’ group. A brain scan revealed key differences in the brains of the two groups, particularly in the ventral striatum, a part of the brain involved in reward, pleasure and addiction.

In this region, the impulsive rats had lower levels of D2 and D3 receptors – molecules that interact with dopamine, a multi-purpose signalling molecule involved in feelings of pleasure.

Lab rats are telling us about how drug addiction happens in the brain.Dalley’s rats were given access to cocaine using a set-up that allowed them to give themselves a hit via a catheter. Sure enough, the impulsive rats gave themselves many more drug infusions than the non-impulsive ones.

So in rats at least, an individual’s impulsiveness, as indicated by the levels of D2 and D3 receptors in their ventral striatum, signposts an inbuilt vulnerability to drug abuse.

Dalley’s work support earlier studies in which mutant rats without any D2 receptors altogether became quickly and strongly addicted to cocaine. In rats, these receptors may act as a molecular conscience, limiting excessive reactions to addictive substances.

And once drug use begins, it triggers other changes in the way the striatum reacts to dopamine. Studies in monkeys have found that as the animals start getting hooked on cocaine, the levels of D2 receptors in their dorsal striatum – next to the ventral part – start to fall, and stay that way for years after they come off the drug.

These results provide a behind-the-scenes look at the molecular changes that turn an impulsive urge to take a drug to a compulsive urge to continue taking it.

It is likely that the receptors play a similar role in our own brains, and their levels are probably controlled by genetic variations. Finding the genes responsible could provide valuable clues for identifying ways of treating addiction, or preventing successful quitters for relapse.

And while cocaine was the drug of choice in this study, Dalley’s results could have implications for other drugs like nicotine (which is equally addictive), or possibly even non-pharmacological addictions like gambling.

 

Reference: Dalley, Fryer, Brichard, Robinson, Theobald, Laane, Pena, Murphy, Shah, Probst, Abakumova, Aigbirhio, Richards, Hong, Baron, Everitt & Robbins. 2007. Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315: 1267-1269.

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The insula – the brain’s cigarette addiction centre

By looking at smokers who have experienced brain damage, scientists have discovered a specific part of the brain that controls addiction to nicotine – the insula. If this area is damaged, a smoker completely loses the urge to smoke.

It is mid-February and we are six weeks into the new year. For most of us, our New Year’s resolutions have long been forgotten and our bad habits remain frustratingly habitual. The things that are bad for us often feel strongly compelling, be they high-fat foods, gambling or alcohol. And nowhere is the problem of addiction more widespread, serious and dangerous than the case of cigarette smoking.

Smoking is the biggest threat to the health of the developed world. Smoking is the leading preventable cause of death in the developed world, and every year it kills five times more people than drugs, suicide, murder, road accidents and HIV combined.

The dangers of smokers are both well-established and well-known, and surveys repeatedly show that the majority of smokers want to quit. But weaning oneself off a substance as addictive as nicotine is not easy.

People often view quitting smoking as a question of willpower – a problem of the mental world. But like all mental processes, addiction eventually boils down to physical matter, to our brains and the chemicals that reside within.

Neurological studies have found that smoking causes long-term changes to various parts of the brain including the dopamine system involved in feelings of pleasure, and the amygdala, involved in emotional responses.

Even cues associated with smoking such as the smell of smoke or the sight of a cigarette, can trigger distinctive patterns of activity in these areas, and are likely to contribute to the urges that smokers feel.

The insula is the brain's cigarette smoking addiction centreNow, Nasir Naqvi and colleagues from the University of Iowa have tracked down the neurons that control the addictive urges of smokers to a part of the brain called the insula.

Located deep inside the brain, the insula is involved in emotion. It collects and processes sensory information from the rest of the body, and translates them into conscious emotional experiences, such as cravings, hunger or pain. And in doing this, the insula could control cravings for cigarettes in response to smoking-related cues.

Naqvi found compelling evidence for this by looking at several smokers who had suffered brain damage, often because of a stroke. Many of these smokers successfully kicked their habits, but in those with damage to their insulas, something more unusual happened.

While most people find quitting a long and difficult process, those with insula damage quit easily and immediately. They never touched a cigarette again, and most importantly, never felt the urge to do so. They completely lost their addiction to smoking and were 22 times more likely to do so than smokers with other types of brain damage.

Naqvi believes that becoming addicted to nicotine causes the insula to change, making smoking just as necessary a bodily need as hunger or thirst. The insula processes information about sights, smells and feelings that relate to smoking and anticipates both the pleasurable effects of nicotine and the negative effects of nicotine withdrawal.

The end result is a strong and conscious urge to smoke, that disappears when the insula is damaged. As one patient said, his body just ‘forgot the urge to smoke’.

But can this knowledge be used to help smokers to quit? Directly changing the insula seems an unlikely step. The major worry is the direct treatments could have knock-on effects other aspects of a patient’s life.

However, Naqvi promisingly found that none of the patients with insula damage lost their urge to eat, or the pleasure of doing so. He suspects that urges like hunger, that are essential for our survival, are controlled by multiple brain networks that act as failsafes should any one fail.

Alternatively, the insula may only control bodily cravings that people develop over time, while other brain regions deal with more instinctive drives.

Nonetheless, the knowledge that the insula is the brain’s nicotine addiction centre could help in indirect ways. Scientists could look for drugs that target neurotransmitters active in the insula. And by monitoring brain activity in the insula, doctors could compare how effective some quitting methods are against others.

In the mean time, smokers should bear in mind that giving up can be difficult but millions of people have successfully done it. And in doing so, they have reduced their risk of cancer, heart disease and many other illnesses.

Reference: Naqvi, Rudrauf, Damasio & Bechara. 2006. Science 315 531-534.

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