2006 Annual Report 4d.Progress report. This report serves to document research conducted under a Cooperative Agreement Trust between ARS and Pom-Wonderful/the Stewart and Linda Resnick Revocable Trust of Los Angeles, CA. In the first study funded by this organization the results that we obtained indicated only minimal beneficial effects of pomegranate juice (POM) on behavior in the aged animals. There were no differences between the groups on any of the motor tests. When examining Morris water maze (cognitive) performance, we performed separate t-tests between the two trial latencies for each group, to determine if the different juice groups significantly improved their performance from Trial 1 to Trial 2, showing improved working memory. Trial 1 measures reference memory while Trial 2 is a measure of working memory. No effects were seen in the high POM group. The low POM juice showed improved working memory (i.e., there was a significant difference between Trial 1 and Trial 2 performance in this group), however, Trial 1 performance in the low POM juice group was worse than the group given water to drink, i.e., the low POM juice group took longer to find the hidden platform on the reference memory trial. Working memory performance was not different between the groups. Therefore, one cannot conclude that the low POM juice had improved performance compared to the water group. There were indications that the muscarinic receptor sensitivity was increased in the striata of the aged animals as we have seen previously with the blueberries. For these reasons we believed that the concentrations used in these studies were too low (.33 % and 3.3%) to see an effect on behavior. However, it was encouraging that both concentrations had an effect on muscarinic receptor sensitivity. We have received additional funding to carry out the behavior and neuronal evaluations again using higher doses of a concentrated extract of the pomegranates. The agreement between ARS and Pom-Wonderful has recently been approved and we will be starting the study within the next two months. Additional details of this research can be found in the report for the parent project 1950-51000-063-00D Nutritional Modulation of Brain Aging and Cognitive Decline. All studies with pomegranate juice were completed in 2005.