Joel Yager, M.D.
Monday, April 8, 2002
What We're Learning About Anorexia Nervosa From Animal Research Written By: Joel Yager, M.D. -------------------------------------------------------------------------------- Research laboratories are busily studying a number of animal models of anorexia nervosa that may ultimately help us prevent these disorders and better treat individuals who succumb to them. Two approaches are particularly exciting: One model of anorexia nervosa developed in laboratory rats is called "activity anorexia". Animals with this condition develop a pattern of exercise, eating and weight loss that resembles behavior patterns of excessive exercise and food restriction seen in many patients with anorexia nervosa. For several decades, researchers have known that when laboratory rats are given unrestricted access to both an exercise wheel and to food, they exercise a great deal and eat enough to keep their weights up they become healthy, well conditioned rats. However, when rats are given unlimited access to exercise but their food intake is restricted to 60 minutes per day, many rats continue to exercise a great deal and may even increase their exercise, expending more calories than they consume. Some lose significant amounts of weight, even to the point of death. The wheel running behavior appears to be self-reinforcing, associated with reward systems in the brain. Research has shown that pre-treating these rats with medications such as fluoxetine, i.e., Prozac, chlordiazepoxide (a so-called benzodiazepine medication such as Librium), or with the amino acid tyrosine often protects them from the effects of unrestricted exercise that is, when theyve taken these substances the treated rats eat in proportion to their exercise and do much better. For some strains of rats there is some debate as to whether hungry female rats actually get more out of increasing their running more than males. Why this might be is mysterious. Differences in sex hormones may determine why the female rats respond differently than male rats to these conditions. Another animal model is purely genetic. Veterinarian researchers have identified a condition in hogs called "thin sow disease". As farmers try to breed hogs that have less fat, theyve noticed that many herds contain a few female hogs who are extremely active, eat little and waste away. Geneticists have become interested in studying the genes of these thin hogs to see if they bear any similarities to genetic patterns now being examined in patients with anorexia nervosa and their families. Other researchers are studying differences in feeding and activity related behaviors in genetically different animals. For example, some research suggests that a variant of the so-called "agouti-protein" gene associated with fat metabolism is associated with some cases of human anorexia nervosa; animals with these variants are being bred and examined to better understand mechanisms associated with the brain hormone melanocortin that may be involved. Other genes thought to be involved in anorexia nervosa are also being studied in animals. What Benefits Might Come From This Work? The activity anorexia research clearly shows that some rats, perhaps affecting females more than males, are prone to eat less if they over-exercise, and that this may even result in death. Presumably, these rats are genetically different from rats who are not prone to such behavior. Therefore, even now, individuals who know that they tend to eat less when they exercise need to be extremely careful about balancing these fundamental behaviors, to minimize their risks of losing too much weight and of putting their lives at risk. The genetic research promises that some day we may be able to identify individuals who are particularly vulnerable for developing anorexia nervosa before it starts. We may be able to develop preventive programs to reduce their risk. The research also suggests that we may be able to develop better medications to help those who develop these disorders, guided by these genetic differences.