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Question: What makes dopamine such a powerful chemical?

Nora Volkow: Dopamine is a chemical substance that serves to send messages between two cells in the brain, and that's, we call neurotransmitters. There are many neurotransmitters and dopamine plays a key role in the areas of the brain that enable a wide variety of functions, best known is movement and when your dopamine cells die, for example, you cannot initiate movement, and that's Parkinson's disease.

But the effects of dopamine go way beyond movement and one of actions, very relevant for drug abuse and addiction, is it modulates the areas of the brain involved with our ability to perceive reward reinforcement and to be motivated by that reward to do actions. So, for example, it's so important that if you can generate through trans-genetic, genetic technologies, you can generate in a mouse that does produce synthesized dopamine. These animals will die of starvation because they don't have the motivation to engage in the behaviors to go and eat the food. You can rescue this animal by injecting dopamine into the areas of the brain that control this. But if you don't to that, these animals will die of starvation. And that really epitomizes how extraordinary important dopamine is. It gives you that energy, that drive to do things.

Now, drugs of abuse, we know that for the past 50 years, all of them, whether it's legal or illegal, they don't make any distinctions over there in terms of the pharmacology, they increase dopamine in specific areas of the brain, of the limbic brain. And this ability to increase dopamine when a person takes a drug is associated directly with what we call rewarding or reinforcing effects. So if you can actually manipulate it in such a way that to interfere with the ability of a drug to increase dopamine, than that drug is no longer pleasurable.

And so that's why dopamine is so important. Understanding why certain drugs can produce addiction and others not. If a drug produces increases in dopamine in these limbic areas of the brain, then your brain is going to understand that signal as something that is very reinforcing. And will learn it very rapidly, and so that the next time you get exposed to that stimuli, your brain already has learned that that's reinforcing and you immediately what we call a type of memory that's conditioning, will desire that particular drug.

Now, these mechanisms are not developed in our brains to take drugs. These mechanisms of dopamine signal reinforcement and once you have experienced it, getting conditioned to it is extraordinary important way for nature to ensure that humans, as well as animals, will perform behaviors that are indispensable for survival. So therefore, it shouldn't surprise us that behaviors such as eating or sexual behavior are linked with increases in dopamine and in the same areas that drugs do it. There are differences though, because natural reinforcers increase dopamine as a function very much of the context. What do I mean by that? If you're hungry, for example, and you get exposed to food, that will increase dopamine much more than if you just finished eating. And so as you eat, the ability of food to increase dopamine goes down and eventually disappears. And because it disappears, you are no longer motivated to eat the food.

Question: How is dopamine related to drug addiction?

Nora Volkow: What happens with drugs though, on the other hand, is they do not decline the ability to increase dopamine. So a person may take a hit of cocaine, snort it, it increases dopamine, takes a second, it increases dopamine, third, fourth, fifth, sixth. So there's never that decrease that ultimately leads to the satiety. And this is believed that then these differences between the normal responses of the dopamine stimuli as it was developed through evolution to serve physiological functions, versus the ways that drugs do it, much more potently, longer duration of action. And it does not decline with repeated administration. It's believed to trigger the adaptations, the plastic changes in our brain, that eventually will lead, in those individuals that are vulnerable, to addiction. To the process of addiction, which is a condition whereupon the person, with repeated administration of drugs, no longer can control his or her ability to decide when they take or they don't take the drug. This is fundamentally a stage where that individual has lost control and has intense drive to compulsively take the drug.

And that's what we call addiction. Not everybody that takes drugs, actually, becomes addicted. We've come to recognize, for example, that approximately 50% of the vulnerability of a person to take, to become addicted is genetically determined. So that vulnerability has a very strong genetic component. It also has other processes that determine vulnerabilities. For example, if you get exposed to drugs when you're very young, very early adolescence, you're much more likely to become addicted than if you get exposed to the same drugs when you're an adult. And this has to do with the fact that the adolescent brain is much more neuroplastic than the adult brain. And as a result of that, a drug, which triggers this adaptation process, is likely to produce these changes faster in an adolescent and it's also the duration of those changes is likely to be much longer lasting in an adolescent than it is an adult. So these are two processes as it relates to addiction.

Recorded on November 6, 2009

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