of dopamine. Later, these same subjects imagined what it would be like to actually vacation in these

of dopamine. Later, these same subjects imagined what it would be like to actually vacation in these places, and rated their imagined experience. Those on L-dopa felt they would be much happier, revealing the power of dopamine to cause changes in our experience of reward. Complimenting these experimental results are studies showing that genetic variation in the expression of dopamine in humans are closely tied to impulsive behaviors and behavioral disorders. Thus, individuals with genetic variants that result in higher levels of dopamine are more likely to engage in compulsive gambling and eating, leading to addictions. The anticipation of heightened pleasure leads these gamblers, eaters, and abusers to want more and more. This work shows that dopamine is necessary for monitoring and guiding our desire for reward, with evidence of individual differences that start with our biology. This is a highly adaptive system. But changes in dopamine can also cause our desire for reward to runaway, like a brakeless trolley. This is a highly maladaptive process. This flip between adaptive and maladaptive that we see within the dopaminergic system is, by now, a familiar brain routine. It provides, I believe, the means to explain all manners of excess, from the desire for food and money to drugs and violence. Obesity and drug addiction are disorders of excess. They are disorders of insatiable desire. There are many paths to obesity and addiction, but all ultimately point to changes in the reward system. In humans born with deficient levels of the hormone leptin, overeating and obesity are common outcomes. When these individuals view images of food during a brain scanning session, they show lower levels of activity in the striatum than non-leptin deficient individuals. The striatum 1s an area that is rich in dopamine and an essential part of the reward system. This may, at first, seem paradoxical: how could those who eat to excess not show an excess of activity in the striatum, and thus, an over-the-top experience of reward upon seeing food? The answer lies in studies of rodents and humans. Whether it is obese rats or obese people, both show compulsive eating, but lower levels of expression of dopamine in the striatum. If you silence a key dopamine gene in rats, you can quickly turn them into food junkies, driven by an unsatisfied wanting system. Overeating, like over-drugging, turns the reward dial down. This is an adaptive response, except when it operates in the mind of a food or drug junky. Though the reward hits are small and unnoticeable, the wanting system remains highly motivated, triggered by the same cues. What food and drug junkies want is more hits, but the reward system isn’t delivering. This causes them to want even more. What the work on obesity and addiction tell us is that independently of how people get started on the path to fulfilling their desires, and whatever leads them to over-consume, consumption loses its luster. The brain is smart: excess is bad and thus the reward systems turns off. But because the wanting or desire system is independent from the reward system, and has evolved insurance against a complete shut down, Hauser Chapter 2. Runaway desire 62 HOUSE_OVERSIGHT_012808