Fishing for Answers to Addiction

By Andy Bodle 07/15/13

In laboratories around the world, scientists are carrying out all kinds of weird and wonderful experiments in the name of addiction research. Does the secret really lie in the aquarium?

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How much do we really know about addiction? The brutal truth is, not a lot. Sure, we've come a long way since the days when "treatment" involved the drunkard's cloak or frying brains, but there are still some fairly hefty gaps in our knowledge. How is it that two people can use the same drug, but only one of them becomes addicted? Why do some people find quitting easier than others? And why does a cure for one person have no effect on the next?

It's heartening to know, then, that in laboratories around the world, geneticists, psychologists, biologists and neuroscientists are carrying out all sorts of weird and wonderful experiments in the name of addiction research.

What's my stake in this? Well, I'm no scientist, but I am deeply passionate about the subject. I've spent four years reading up on evolutionary psychology for my blog, Womanology, which is an attempt to fathom the mysteries of the dating world, and I'm a volunteer with Science London, a charity that organizes social events with a scientific twist. I've also battled my fair share of demons: In my 43 years on this earth, I've been hooked on gambling, pornography, tobacco, video games, alcohol and cocaine. (I'm pretty sure I'd have been addicted to sex, too, if I'd ever managed to track down a reliable supplier.)

Two things could trigger a relapse: a small dose of the stimulant or a stressful incident, such as a pinching of the tail.

So when I heard that Science London was putting on a talk called "Addicted Fish: How useful are animal models in understanding the molecular and cellular mechanisms that underlie addiction?" I signed up like a shot.

Can fish really tell us anything about human behaviour? Whoever heard of a herring hooked on heroin?

The speaker was Dr. Matt Parker, a geneticist at Queen Mary University London (and until last month, it seems pertinent to mention, a 30-a-day man). He began, in front of a small but committed crowd in a room above a pub in central London, by addressing the question on everyone's lips: Why fish?

Well, they're not actually as different as you might think. You've no doubt heard the statistic that humans share 98% of their genes with chimpanzees. Well, it turns out that we also have around 85% of DNA in common with mice and rats—and a surprising 70% with zebrafish. The basic workings of most vertebrates, it turns out, are pretty similar.

The main sticking point for addiction research is that there's only so much you can carry out on humans. You can perform tests (within limits) on people who are already addicted, but you can't ethically make someone addicted and then see how their brain changes. (Some would argue that you can't ethically do this to any living beings, but I'm not going to start that discussion here.) So for a long time, the experimental subject of choice has been that old standby, the rat.

It soon emerged that rats, like people, can develop pernicious habits. Scientists have bred coke-fiend rats, skaghead rats, chain-smoking rats and dipso rats, and they all exhibited symptoms similar to those seen in humans: anticipation, response to conditional cues (things associated with the stimulant, such as flashing lights), withdrawal symptoms and relapse.

They seemed to go through the exact same stages of dependency, too: irregular use, regular use, habitual use, cravings, a phase where they develop tolerance to the stimulant and experience withdrawal when denied it, and finally, the compulsive drug-seeking stage, when they will choose the drug ahead of more important things, such as food and sex.

In the tests, many of them at Cambridge University, a number of techniques were used to deliver the drug. Sometimes the rats would have to press a lever to obtain the stimulant; sometimes they would have to push their noses through a specific hole after a light flashed on.

Just as with humans, some rats found their habit harder to kick than others. When the scientists introduced a punishment alongside the stimulant—an electric shock, for example—many of the rats stopped indulging. But 20%-25% of them continued pressing the lever and getting their hit, even though they knew there was a big down side. They'd found their rat addicts.

And interestingly, just as in humans, two things could trigger a relapse: a small dose of the stimulant (how many ex-smokers have learned the reality behind the statement "Just one won't hurt"?), or a stressful incident, such as a pinching of the tail.

Zebrafish, tropical freshwater fish popular with aquarium keepers, have several advantages over rats. First, they have more offspring—the female produces hundreds of eggs in each clutch. Second, they're hardy, and can survive more genetic "meddling" than mammals. And finally, the fertilized eggs of the zebrafish are transparent, and develop in water, outside the mother's womb, which makes it easier to see what's going on from a developmental perspective. In fact, the science community is enjoying something of a love affair with the zebrafish, using it in research into areas as varied as cancer, genetics, neurobiology, teratology and stem cells.

But the crucial question for us, surely, is: Can fish get addicted? Well, fish can't press levers, so Dr. Parker and his team had to be a little more imaginative with their delivery system. But before long, they'd established that zebrafish, just like humans and rats, were partial to a wide range of stimulants.

There has been much debate about how much of the "addictive personality" is heritable and how much is down to environment. While the genetics involved are highly complex, Dr. Parker and company can now say with certainty that there is a large genetic component to addiction—for nicotine, at least—and have a much better idea about the specific genes involved.

Many theories had been circulating as to which personality traits are good indicators of a predilection to addiction, with candidates including neuroticism, extraversion, impulsivity (a tendency to act without thinking), novelty-seeking (a propensity to boredom, and the frequent desire for new and varied experiences), and risk-taking. But no one had ever established definitively which, if any, of these characteristics was actually closely linked with addiction.

So Dr. Parker and company observed some zebrafish from birth, rated them for various personality traits, then tried to get them hooked. And what they found was that in zebrafish, only one characteristic was strongly correlated with an addictive nature.

"Impulsivity," Dr. Parker concluded," is the closest thing we have to a causal factor for addiction."

In other words, science now has an important new weapon in the fight against addiction. There's no guarantee that the finding will be replicated in humans. And there's still plenty more work to be done before this research produces any useful results. But it does create the possibility of a future where we can spot the people most likely to develop harmful addictions, and perhaps make more of an effort to steer them away from dangerous substances. It's also a new important step in the direction of treatment tailored to the individual, which is the approach increasingly being favoured by the medical establishment. Finally, as Dr. Parker told me when I spoke to him afterwards, it may also help in identifying problems with relapse and withdrawal.

"It's unlikely that we'll ever be able to say we've 'beaten' addiction," he said. "It's such a complex set of behaviors—and we know that many addicts never do, and never will, find their way into the system. We hope that our research, and similar research to come, may put us in a better position to help people who want or need to engage with treatment services."

If that day does come to pass, spare a thought for the little chap without whom it could never have happened: the zebrafish.

Andy Bodle is a UK-based journalist and blogger who last wrote for The Fix about quitting cocaine.

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Andy Bodle is a journalist and scriptwriter from London who blogs about the science of dating. Find him on LinkedIn and Twitter.