A specific protein found in the brain of rats appears to be intricately involved in regulating the animals' response to an amino acid-deficient diet, according to researchers at the University of California, Davis, School of Veterinary Medicine. This is the first reported evidence of the protein's influence over a certain chemical-sensing mechanism in the brain and may have implications for treatment of anorexia, a serious eating disorder in humans associated with loss of appetite and decreased food consumption. "The protein we studied has been shown to have great potential for treating strokes, epilepsy and other seizure disorders, but this is the first evidence that it also modulates the animal's response to a dietary deficiency," said UC Davis neurophysiologist Dorothy W. Gietzen. She will present the findings at 9:30 a.m. Friday, Nov. 18, at the annual meeting of the Society for Neuroscience in Miami. Gietzen and colleagues found that when the brain protein known as the NMDA (N-methyl-D-aspartate) receptor was chemically blocked or inactivated, the eating behavior of the rats receiving an amino acid-deficient diet was affected. They continued to eat almost as much as they had previously of the regular, balanced diet, rather than suddenly decreasing their food intake, which is their typical anorectic behavior when fed an amino acid-deficient diet. Amino acids, the chemical building blocks for proteins, are critical for normal body functions, such as repair, maintenance, growth and reproduction. Certain amino acids must be eaten every day, because the body cannot make or store enough of these compounds to meet daily needs. If insufficient amounts of these amino acids are consumed, the body's internal chemistry becomes unbalanced and its normal functions interrupted. While anorexia or appetite loss associated with amino acid imbalance has been reported for years, the mechanisms that cause this anorexia are not yet fully understood. It is known that there is a specific area of the rat's brain that monitors the body's amino acid content. This delicate, chemical-sensing system enables the animal to detect and respond to amino acid deficiency. For example, it has been shown that a rat can recognize an essential amino acid at levels as low as 100 parts per million. The ability of rats to respond to amino acid imbalance by decreasing food intake also has been well-established by previous research. Normally, when rats are fed diets containing insufficient amounts of amino acids, the animals recognize the imbalanced diet about 30 minutes after eating and dramatically decrease their intake of that diet for several days in order to select a more nutritionally balanced diet. If an alternative feed is available, the rats will eat almost any diet that restores amino acid balance, even one that has been altered to taste very bitter. Therefore, the rats' responses to the deficiency can be monitored by measuring decreases in food intake. In this study, 19 male albino rats were observed. Under anesthesia, the rats were surgically fitted with guide tubes aimed at the brain area known as the prepiriform cortex or PPC, believed to contain the amino acid-sensing mechanism. After recovering from the anesthetic, the rats were fed a regular diet for at least one week, during which baseline food intake measurements were recorded. During the experiment, 30 minutes before the imbalanced diet was offered to the rats, a drug that is known to block the NMDA receptor was injected into the brains of the 11 test rats. The blocker drug is called AP5 (D(-)-2-Amino-5-phosphonopentanoic acid). Eight rats in the control group were given the same volume of a solution that would not affect the NMDA receptor. When fed an amino acid-imbalanced diet, rats usually eat about half their usual food. As expected, the blocker-free rats ate 55 percent of their normal consumption. However, the rats receiving the NMDA receptor blocker did not demonstrate such a loss of appetite. They ate fully 88 percent as much as they had been eating of the balanced diet. Although this study involved an animal model, the results suggest that drugs similar to the NMDA receptor blocker might have some use in the treatment of certain types of anorexia in humans. "Having thus demonstrated the NMDA receptor's role in regulating the anorectic response to dietary deficiency, we now want to take a look at its role in the learning process," said Gietzen. Animals that need to select a balanced diet also need to learn which diets should be avoided, she said. Therefore, the ability of the rats to remember the imbalanced diet will be tested after treatment with an NMDA receptor blocker, such as was used in this study. Collaborating with Gietzen on the study were Ban G. Truong and Bickley Dang, both student research interns in the School of Veterinary Medicine. Funding for this research was provided by the U.S. Department of Agriculture and the National Institutes of Health. Purified L-amino acids used in the test diets were donated by Ajinomoto Inc., USA.