DEFINITIONS OF TERMS Dopamine A compound that sends signals from one neuron to another, and is made from the amino acid tyrosine. Dopamine reward pathway A circuit in the brain that when activated leads to feelings of pleasure. Rewarding experiences such as food and sex stimulate the dopamine reward pathway. Nucleus accumbens (NAc) A region of the brain that is involved in reward, pleasure, addiction, fear and laughter. Prefrontal cortex (PFC) The anterior part of the brain (located below the forehead) that plays a role in personality, decision-making and social behavior. Ventral tegmental area (VTA) A group of neurons that is the start of the dopamine reward pathway. Dopamine is released from the VTA to the NAc and PFC. For a complete list of defined terms, see the Glossary. LESSON 3.4 WORKBOOK Can you become addicted to food? In this lesson we will examine yet another complicating factor that can thwart our intentions to maintain a healthy weight the similarities between how our brain behaves when confronted with food and how it behaves when confronted with drugs of abuse. The realization that there are many commonalities between the addicted brain and the obese brain is a recent one, and it has significant implications for future treatments of obesity. The dopamine reward pathway The various feeding and satiety messages we learned about in the previous lesson do not single-handedly determine what and when we eat. Almost everyone has inhaled a mouth-watering dessert even on a full stomach; we often eat because food is in front of us. It smells good, tastes good, and looks good! We might eat because it is the right time of day, we are celebrating, or we are trying to overcome sadness. After a meal, pleasant memories reinforce our appetite, giving us the desire to eat. The dopamine reward pathway is responsible for our feelings of pleasure Our desire to eat is controlled by the dopamine reward pathway, which originates in an area of the brain called the ventral tegmental area (VTA). The dopamine neurons in the VTA send connections to the nucleus accumbens (NAc) and the prefrontal cortex (PFC). Don t worry if you don t get these terms right away, we ll be discussing the reward pathway for the rest of this lesson. 129
LESSON READINGS Dopamine Reward Pathway PFC NAc VTA Pleasurable s1muli Figure 1: The dopamine reward pathway is made up of the prefrontal cortex (PFC), nucleus accumbens (NAc) and the ventral tegmental area (VTA). The connections between the VTA, NAc and PFC are collectively called the reward pathway because they are activated during pleasurable experiences, such as eating, during sex, consuming drugs of abuse or when given praise. Because the same reward center in the brain is responsible for positive feelings after using drugs and after eating, overeating may in fact impact the brain like abusing a drug. Eating is associated with dopamine release in the reward pathway, and the amount of dopamine released during a meal can be used to predict how pleasurable the experience of eating was. As expected, different foods produce different levels of dopamine release, leading to different levels of pleasure from a meal. Typically, food that is high in sugars and fats are deemed more pleasurable, though this varies between people. Also as expected, the amount of dopamine released in the nucleus accumbens is reduced as a meal continues, meaning that the first bite of a food will be the most pleasurable, and all following bites will get more and more boring! Food cravings are related to the dopamine reward pathway Dopamine regulates food consumption not only because it acts on the reward pathway while eating, but also because we can be conditioned to stimuli that then drive our motivation to consume foo For example, whenever you sit down to watch a movie you may feel the urge to eat popcorn. One of the first descriptions of a conditioned response was by a scientist named Ivan Pavlov, who showed that after dogs were exposed to repeated pairings of a tone with a piece of meat, the tone itself would cause the dogs to salivate even when no food was present. It has since been discovered that this conditioning increased dopamine release in the reward pathway upon associations with foo Figure 2: Pavlov conditioned dogs to expect food every time a bell was rang. This increase in dopamine in the reward pathway is the cause of the intense food cravings we all experience. Like Pavlov's dogs, humans can be conditioned to associate eating with stimuli that have previously been tied to foo For some people, it is the need to drink coffee every morning, for others it is the need to finish the day with a sweet dessert. Sometimes we can pinpoint the root cause of the craving, but other times we don t know what sets these cravings off. 1. Which best describes the dopamine reward cycle? A circuit between organs of the body and regions of the brain. A series of chemical reactions that release energy. Regions of the brain that are connected by neurons. Neurons in the hypothalamus that release signaling proteins. 2. Pleasurable stimuli: Activate the dopamine reward pathway. Can become addictive. Lead to dopamine release. All of the above. 130
DEFINITIONS OF TERMS Adrenal glands Glands that sit on top of the kidneys that produce hormones that help control heart rate, blood pressure, and stress reactions. Cortisol A steroid hormone that is released in response to stress, and increases blood glucose, suppresses the immune system and speeds up metabolism. For a complete list of defined terms, see the Glossary. LESSON READINGS Stress triggers overeating Stress can play a particularly critical role in overeating. Moderate stress will stimulate appetite and lead to overeating in a variety of mammals, from rodents to humans. This suggests that there is some stressevoked biochemical signal that modifies the reward pathway to trigger overeating. In the short-term, stress hormones released from the brain actually suppress the appetite. If stress persists, glands sitting on top of the kidneys, called adrenal glands, will release a stress hormone called cortisol. Cortisol is the stress hormone that is responsible for increasing appetite, though the reason why is not yet completely understoo Stress can also affect food preferences, making you want to eat food that is high in fat and sugar. These foods in turn will activate the dopamine reward pathway, giving us a sense of pleasure, and perhaps combatting our stress for a short period of time. Some research has suggested that men and women deal with stress differently. For example, women are more likely to turn to food when they are stressed, and men are more likely to consume alcohol or smoke. Figure 4: Nature vs. nurture: are some people more likely to be addicted to drugs or foo Figure 3: Eating high calorie, sweet and fatty foods is a common response to chronic stress. Can you inherit an addiction? People suffering from addiction or from obesity are often stigmatized as having little will power. Yet addiction and obesity are complicated diseases that result in structural changes in the brain that are difficult to remedy. A portion of the vulnerability to addiction may be attributed to genetic differences. For example, addictive behaviors tend to run in families, yet the contribution of genetics and environmental factors is complex and an area of active research. Just as the genetic and environmental influences in addiction vary between cultures and people, so does the interaction between genetics and environmental conditions leading to obesity. Understanding the relationship between innate (nature) drive for food and learned (nurture) associations that lead to obesity is an area of intense research. But one thing is clear, being addicted to substances or foods leads to dramatic changes in the structures of the brain that perpetuate the cycle of addiction. 3. Long term stress results in: Suppression of the appetite. Release of dopamine. Feelings of pleasure. Release of cortisol. 131
DEFINITIONS OF TERMS Inverse Opposite in direction or effect. For a complete list of defined terms, see the Glossary. LESSON READINGS This is your brain on obesity Why does the brain 'promote' obesity? Our reward pathways are particularly sensitive to high-calorie foods containing sugar and fat. This makes sense evolutionarily, because as hunters and gatherers we often failed to find food, and sometimes had to wait several days between meals. So craving calorie rich foods offered a survival advantage; it was in our best interest to seek high calorie foods, so our bodies adapted a mechanism that would find high calorie foods rewarding, motivating us to eat them. For a greater part of human evolution, sweet taste was associated with only fruits. Now that we live in a time when sugars and fats are abundant, the dopamine reward pathway can backfire. Instead of being there to protect us from starvation, our preference for high calorie foods can harm us by leading to weight gain and obesity. Changes in the dopamine reward pathway Eating, smelling and seeing images of foods can lead to increased dopamine release in the reward pathway in the brain. Some research suggests that the magnitude of the dopamine response is associated with an individual s body mass index (BMI). In general, lean individuals have an increased dopamine response when stimulated with food relative to overweight or obese individuals. This indicates that obese people may develop a tolerance to the activation of the reward pathway in response to consuming foo Figure 6: Dopamine is a simple molecule, that when released gives us feelings of pleasure. Figure 5: In addition to protecting us from starvation our food drive can promote obesity when an abundance of calories are available. This blunting of the reward pathway in obese individuals may be due to a reduction in dopamine receptors present on the neurons that make up the reward pathway. In one study, the number of dopamine receptors in the reward pathway was inversely related to BMI in an obese population. The idea being that over time overconsumption of food causes a decrease in sensitivity of the reward pathway, which sets up a vicious cycle of needing excess food to feel satisfie 4. We have evolved to prefer lowcalorie, micronutrient-light foods. True. False. 5. A reduction in dopamine receptors in the dopamine reward pathway would: Numb the feelings of pleasure from foo Heighten the sense of pleasure from foo Increase sensitivity of the reward pathway. Lead to severe weight loss. 132
STUDENT RESPONSES Some scientists have attempted to make an anti-obesity prescription drug by targeting the reward pathway. What sort of side effects would you expect the drugs to produce if they are successful in inhibiting the reward pathway? Would these drugs work for reducing obesity? Why or why not? Remember to identify your sources 133
TERMS For a complete list of defined terms, see the Glossary. TERM Adrenal Glands Cortisol Dopamine Dopamine Reward Pathway Inverse Nucleus Accumbens (NAc) Prefrontal Cortex (PFC) Ventral Tegmental Area (VTA) DEFINITION Glands that sit on top of the kidneys that produce hormones that help control heart rate, blood pressure, and stress reactions. A steroid hormone that is released in response to stress, and increases blood glucose, suppresses the immune system and speeds up metabolism. A compound that sends signals from one neuron to another, and is made from the amino acid tyrosine. A circuit in the brain that when activated leads to feelings of pleasure. Rewarding experiences such as food and sex stimulate the dopamine reward pathway. Opposite in direction or effect. A region of the brain that is involved in reward, pleasure, addiction, fear and laughter. The anterior part of the brain (located below the forehead) that plays a role in personality, decision-making and social behavior. A group of neurons that is the start of the dopamine reward pathway. Dopamine is released from the VTA to the NAc and PFC. 134