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Molecular Psychiatrist Eric Nestler It's a Hard Habit to Break

Oct 1, 2001 5:00 AMNov 12, 2019 5:37 AM


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These days it seems as if everyone is addicted— not just to heavy drugs such as cocaine but also to newly claimed obsessions such as eating, gambling, and the Internet. In his lab at the University of Texas Southwestern Medical Center, molecular psychiatrist Eric Nestler is making progress in understanding the nature of addiction and the strong similarities between different kinds of cravings. His studies show how a protein called delta-FosB modulates the brain's sensitivity to drugs, raising hopes of medical treatments that could set addicts free. Nestler discussed the science of need with Discover reporter Jocelyn Selim.

What are the common elements of various kinds of addictions? Research over the past 20 years has shown that addictive drugs all produce the same net effect, which is to stimulate a "reward pathway" in a part of the brain that controls the release of dopamine. The differences come about because each drug also triggers responses elsewhere. Heroin affects the spinal column and the brain stem, slowing the respiratory rate; cocaine speeds up the heart and so can cause a heart attack.

What about people who say they're addicted to behaviors such as gambling, sex, or surfing the Internet? There is growing evidence that these natural addictions— compulsive behaviors connected to things other than drugs— all probably have at their core the same brain reward pathways. In fact, recent brain-imaging studies show that the nucleus accumbens, the brain area associated with drug addiction, lights up both in compulsive gamblers and in people or animals shown sexual stimuli.

Do you regard tobacco, alcohol, and marijuana as "gateway" drugs? There are people who use softer drugs who would never try the illegal ones. But because the reward mechanisms are so much the same, there is something to the gateway theory. Marijuana is obviously addictive because some people use it compulsively. Cannabinoids, which cause the marijuana high, hang around in the body so long that withdrawal occurs imperceptibly. If you give a cannabinoid-blocking compound to a marijuana addict, all of a sudden you see severe withdrawal syndrome.

Can a drug be addictive if it produces no withdrawal symptoms? In theory, yes. With the natural addictions— gambling, eating, etc.— you don't experience any physical withdrawal, but you do get cravings. Cocaine doesn't produce strong physical withdrawal symptoms, but it is highly addictive. Conversely, there are a lot of medications, such as the heart medication Inderal, that cause a clear physical dependence but are nonaddicting.

How much of addiction is genetic and how much of it is social? Epidemiological studies tell us that about half the risk for addiction is genetic. And the degree of genetic vulnerability seems to be roughly the same for the various types of drugs— alcohol, heroin, cocaine. To put the numbers in perspective, a 50 percent genetic risk is higher than for type II diabetes or hypertension, which we often think of as genetic diseases.

Why do we have this susceptibility? The dopamine pathway probably evolved to provide an emotional reinforcement for certain choices an animal makes about food, sex, and social interaction. Drugs of abuse came along and commandeered this pathway with a force and persistence that's not seen in the natural world.

Will there ever be a medical cure for the problem of drug addiction? We have to be able to do better than we're doing now. Addiction and compulsive behavior are responsible for so many bad things in society: crime, loss of life, AIDS, lung cancer. I think rehab programs alone are doomed to failure until we understand the fundamental biology. Then we'll be able to develop treatments and preventive measures. Thankfully, we should have prototypes within five years.

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