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The Dopamine Connection
Broadcast starting week of July 7, 2004

Sex, gambling, drug use, extreme sports. Behind ALL these thrills lurks a brain chemical called dopamine. In this hour, we explore The Dopamine Connection. Guests include Dr. Daniel Weinberger, chief of the Clinical Brain Disorders Branch of the National Institute of Mental Health; Dr. Hans Breiter, assistant professor of psychiatry at Harvard Medical School and an expert in brain imaging; Dr. Helen Fisher, a research professor in the department of anthropology at Rutgers University, whose new book is Why We Love: The Nature and Chemistry of Romantic Love; and Mark Decena, the director and co-writer of Dopamine, the movie. Plus, we'll hear about a fascinating study that shows a link between the dopamine medications given for Parkinson's disease and compulsive gambling.

Host Dr. Fred Goodwin begins with an essay in which he asks, "Why would we do a whole show on a single brain chemical?" The answer is, because focusing on dopamine allows us to explore the connection between the complex inner working of the brain and our moods, behaviors, and, even, personalities.

Dr. Goodwin says his own research career was more-or-less launched by dopamine. At the time, there was a theory that depression was caused by low levels of another neurotransmitter, norepinephrine. He and his colleagues decided to test this by giving L-dopa -- just discovered as a treatment for Parkinson's disease -- to depressed patients. Why L-dopa? Because when it reaches the brain, it is converted first to dopamine, and then, in some places, to norepinephrine. They were surprised to find that in those prone to bipolar mood swings, L-dopa often triggered mania. Was it the dopamine or the norepinephrine? Later, he tested this and reasoned that the original theory was wrong -- dopamine, not norepinephrine, was the villain. They formulated the dopamine hypothesis of bipolar disorder -- that is, that dopamine is elevated in mania and reduced in bipolar depression.

Now, this theory can be tested directly in bipolar patients using techniques covered in the show today, such as brain imaging. And these new direct observations are leading to the development of a whole new generation of drugs -- more specific and hopefully more effective than the ones that launched the whole search in the first place. This is a great example, Dr.Goodwin says, of how science progresses.

Then, The Infinite Mind's Marit Haahr reports on a fascinating study that shows a possible link between the dopamine drugs given for Parkinson's disease and compulsive gambling. If a change in dopamine levels can turn a thrifty doctor into a high-stakes gambler, that's important evidence of the biological underpinnings of a disorder often stigmatized as a personality flaw.

The story opens with Bruce, an anesthesiologist from Memphis, Tennessee who retired on disability because of Parkinson's disease in 1997. He says he was always a frugal person, and gambling never held any interest for him. On a 1998 trip to Las Vegas, his family was surprised and a little troubled to find him glued to a video poker machine. Bruce, who didn't want us to use his last name, says that once he won that first jackpot, all he could think about was winning again. Over the next five years, Bruce lost between $150,000 to 200,000 on video poker and slots.

Across the country in Arizona, neurologist Mark Stacy was hearing similar stories from some of his patients at the Mohammed Ali Parkinson Research Center. He says, "I saw two patients in the course of my fairly busy practice in Phoenix who came in and said, 'You know doctor, I need to talk to you about something. It's been devastating to our family and personally devastating.' Both were similar stories -- both had lost a huge amount of money in the previous three months." Checking their records, Dr. Stacy noticed that three months earlier, he had increased their doses of a medication that stimulates the dopamine receptors in the brain. Dopamine helps direct both muscle control and balance, but Dr. Stacy started thinking about dopamine's other roles in the brain --- which have to do with motivation, reward, pleasure and addiction. Dr. Stacy began to wonder: Could there be a connection to the medications they were taking for their Parkinson's disease? Could gambling actually be a side effect?

Eager to test his hypothesis, Dr. Stacy conducted a survey of about eighteen hundred Parkinson's patients. He found nine who had developed compulsive gambling problems leading to major financial losses. All of them were taking high doses of dopamine agonists, the drugs that stimulate the receptors. When doctors lowered their medication, the patients' urge to gamble was reduced. Bruce, who was one of many people to contact Dr. Stacy after his study was published in the journal Neurology, describes what happened when he stopped taking the medication in question (a dopamine agonist called pramipexole): "It was sort of a revelation to me... Sure enough my attitude did change. I made a 180 degree turn around. I didn't want to gamble, and I reflected on how foolish I'd been."

Dr. Goodwin is then joined by Dr. Daniel Weinberger, chief of the Clinical Brain Disorders Branch of the National Institute of Mental Health. His work on the genetics of brain chemistry and of mental illness was named the #2 scientific breakthrough of 2003 by Science magazine.

Dr. Weinberger begins by saying that dopamine is a chemical in the brain that sends messages from one cell to another. What makes it so interesting to neuroscientists, psychologists, psychiatrists, and neurologists is that it seems to be critical for reward reinforcement and motivation behavior, and this translates into abilities and difficulties in many different areas of life, from drug addiction to thrill-seeking to sex-seeking to psychosis to Parkinson's disease and probably to anxiety and mood as well. At the cellular level, scientists now believe that dopamine focuses the attention of the cell, in a sense serving as a filter, targeting important information from a noisy background.

In a larger sense, dopamine participates in learning and reward and the experience of pleasure. It focuses the attention of the cell so that reward can be experienced -- one cannot learn if one is not rewarded. Dr. Weinberger and Dr. Goodwin then discuss the role dopamine may play in depression, since people with depression do not experience reward. Certain drugs that treat depression target the dopamine system, and the doctors theorize that these drugs may be allowing the patient to experience reward once again, thereby creating a sort of cascade effect that helps alleviate the depression.

They then discuss how dopamine functions in healthy people when, for example, they are hungry and see a meal. Dr. Weinberger says dopamine cells are turned on either when reward is around the corner, that is, in anticipation of reward, or when an experience is more rewarding than a person expects it to be. So, if you have just eaten an enormous meal and you see your favorite food, you're dopamine cells will not be turned on, since they are already satiated. But if you are hungry and you see your favorite food, or if you see a food you love but don't get too eat very often, it's very stimulating to dopamine cells. He says this is important in learning because learning is much more encouraged by intermittent reinforcers. If you're constantly reinforced, being told "great job, great job, great job," it loses its value, in part, researchers think, because it loses its access to dopamine neurons.

Dr. Weinberger then talks about addiction. He says all forms of addiction, from drug abuse to cigarette smoking to gambling, seem to target the dopamine system, adding that not everyone is affected in the same way -- some people seem to have a genetic predisposition toward addiction. He says the problem with drugs like amphetamine or cocaine is they cause a massive increase in dopamine in the brain. A great, very positive experience may cause a 30-40 % increase in the amount of dopamine between cells. When you take a drug like amphetamine or cocaine, you get a several thousand-fold increase in dopamine between cells. He says, "It's a huge sledgehammer of a message like, 'Wow! This is something I want to experience again!'" So it becomes very difficult to resist that experience. Plus, if you are a chronic user, when you are off the drug, you don't just go back to a normal level of dopamine, you undershoot, so the contrast is even greater.

Next, they discuss thrill-seeking behavior. It seems that dopamine is not set to the same level in everyone's brain -- there seems to be genetic variation. This can affect how much pleasure one gets from thrill-seeking. For example, on a roller coaster, you get a surge of dopamine -- it's thrilling, it's stressful, if you like roller coasters, you get a charge out of it. That's the dopamine response to something rewarding and reinforcing. But not everyone's dopamine system is equally responsive, and this could have something to do with how much you want to get back on the roller coaster. Some people don't want to get off them, some never want to go on one again.

To contact Dr. Weinberger, please write to: Dr. Daniel R. Weinberger, Director, Genes, Cognition and Psychosis Program, National Institute of Mental Health, IRP National Institutes of Health, Room 4S-235, 10 Center Drive, Bethesda, Maryland 20892. Or visit: http://cbdb.nimh.nih.gov.

Dopamine plays a crucial role in motivating and rewarding our behavior. But what do we actually SEE when we look at how it works inside the brain? Dr. Goodwin then interviews Dr. Hans Breiter, assistant professor of psychiatry at Harvard Medical School and an expert in brain imaging.

Dr. Breiter has been studying the reward circuitry in the brain, which involves dopamine neurons and dopamine-producing regions of the brain. He says these reward systems were first discovered in rodents -- researchers found that when they placed an electrode in a certain part of a rodent's brain, the animal would repeatedly press a key to deliver electrical stimulation to that area. With modern imaging techniques, we're now able to see these same circuits in the human brain, and we can begin to understand the systems that underlie motivation. He says, "These systems underlie what is at the core of what you might call free will, what is that core of what drives us to do anything at all."

Dr. Breiter has been using functional magnetic resonance imaging (fMRI) to map this reward circuitry in human beings. He and his colleagues started with cocaine addicts and mapped the regions of the brain that became activated during the rush (the reward) and during craving. They then did the same for people experiencing monetary rewards and heterosexual men looking at beautiful faces. They found the same regions of the brain were activated in all these cases, which shows that it is a generalized system, applicable to all kinds of reward behavior.

To contact Dr. Breiter, please write to: Dr. Hans Breiter, Assistant Professor of Psychiatry, Massachusetts General Hospital, 149 13th Street, NMR Ctr., 2nd Floor, Charlestown, MA 02129. Or visit: http://www.nmr.mgh.harvard.edu.

Is love "Chemistry… or Chemical?" That's the question at the heart of Dopamine, the movie. At the 2003 Sundance Film Festival, Dopamine won the Alfred P. Sloan Prize, awarded for the compelling treatment of topics in science and technology. Mark Decena, the director and co-writer joins Dr. Goodwin. Also with them to discuss the science of love is Dr. Helen Fisher, a research professor in the department of anthropology at Rutgers University. Her new book is Why We Love: The Nature and Chemistry of Romantic Love. Dr. Fisher is becoming a regular guest; she's joined us previously for shows on Romance, Sexual Attraction, and, recently, Cheating.

Decena begins by describing the movie, which focuses on two characters, Rand and Sarah, who have opposite ideas about love. Rand thinks it is all chemical -- just a series of reactions in the body -- and Sarah thinks it is much more than that, something magical.

Dr. Fisher says that, from her perspective, Decena got the science right. She and her colleagues put 40 people who were madly in love into an fMRI brain scanner and found some of the brain circuitry of romantic love, and, indeed, one of the areas that becomes active is a part that actually makes dopamine and "sprays it like a sprinkler over much of the brain." As for the question of is it chemistry or is it love, she says, "it's both, it's all of the above." She compares it to a Beethoven symphony -- even if you know all the notes, you still reel when you hear it. She says, "Just because you know the chemistry of something doesn't mean that it isn't also a magical, mystical, almost cosmic experience."

Dr. Fisher continues, saying that love is not new -- it has been around for millions of years. It's a basic drive that evolved to allow us to focus our mating energy on just one person and therefore conserve mating time and energy. Decena says that many people who have seen the film have asked him whether there is a danger that we will be able to control love through chemicals. Dr. Fisher says this is an unrealistic fear. From example, you can take cocaine and drive up dopamine and not fall in love. It's a complex system. We all have the wiring in the brain and capacity for falling in love, yet you can go years without falling in love, even when you want to, and that's because there's a huge cultural component which you can't control with drugs or chemicals. She concludes, "We are never going to be able to create a love pill."

To contact Dr. Fisher, please write to: Dr. Helen Fisher, Department of Anthropology, Ruth Adams Building, 131 George Street, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901-1414. Or visit: http://anthro.rutgers.edu.

To order Why We Love: The Nature and Chemistry of Romantic Love, click here.

To learn more about Dopamine, the movie, or to contact Mark Decena, please visit: http://www.dopaminethemovie.com.

Finally, commentator John Hockenberry meditates on human beings' continual striving for reward. He says, "...after all the brain gravy experiments are done and dopamine levels are calculated for every addiction, every sociopathic criminal act, every romantic experience, every lottery winner, and frenetic passion-seized artist, we get back to the same human puzzle. Humans seek happiness."

- Marit Haahr

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