2005 Annual Report 4d.Progress report. This report serves to document research conducted under a Reimbursable Cooperative Agreement between ARS and the University of Maryland - Baltimore County (UMBC). Exposure to heavy particle irradiation produces neurochemical and cognitive deficits in young animals that are characteristic of much older animals. As a result, it has been suggested that exposure to heavy particles can produce “accelerated aging.” In collaboration with scientists from the University of Maryland, Baltimore County (UMBC), we found that the doses of 56Fe (irradiated) particles needed to affect neurobehavioral endpoints decrease according to the age of the rat. For both measurements of anxiety, using the elevated plus maze, and responsiveness to environmental contingencies, using operant responding on an ascending fixed-ratio schedule, older animals are more susceptible to the effects of irradiation than younger animals. The results also suggest that the interaction between age and exposure to 56Fe particles is not linear. The greatest effect of irradiation was seen with the middle-aged animals; i.e., those that were irradiated at 7-8 months of age. As shown most clearly with elevated plus maze performance, the effect of radiation of the middle-aged animals was to change their level of performance to that of the non-irradiated older animals. Exposing older animals (17-months) did not appear to produce a further deterioration in performance. These findings suggest that age may be a risk factor for the behavioral effects of exposure to heavy particles. The effects are not necessarily linear (i.e., middle-aged rats seem more susceptible to the deleterious effects of 56Fe particle exposure than young or very old animals). Maintaining rats on diets containing antioxidant phytochemicals (blueberry and strawberry extract) can provide a significant degree of radiation protection, depending upon the specific diets and neurobehavioral endpoints. Maintaining rats on diets containing blueberry or strawberry extract at the time of radiation can prevent the occurrence of both the acute and late degenerative changes that result from exposure to 56Fe particles. Both strawberries and blueberries rank high in their ability to scavenge free radicals. The observation that they are capable of ameliorating the effects of exposure to 56Fe particles is consistent with the observation that exposure to HZE – heavy ion particles, produces oxidative stress and that oxidative stress in the central nervous system may play a role in mediating the neurobehavioral consequences of irradiation. The data, however, indicate that the effects of antioxidant diets on the neurobehavioral effects of exposure to 56Fe particles varies as a function of diet and endpoint. While both blueberry and strawberry diets were equally effective in preventing the 56Fe particle-induced disruption of dopamine release, the amelioration of the behavioral effects varied by diet. The strawberry diet was effective in preventing the late degenerative changes producing decreased operant responding on an ascending fixed-ratio schedule. In contrast, the effects of the diets on the deleterious effects of exposure to 56Fe particles on spatial learning and memory varied as a function of the specific task and the specific brain region mediating the task. Latency performance in the Morris water maze depends upon the integrity of the striatum, whereas spatial learning performance with the platform removed on the probe trials is a hippocampally-mediated task. The diet containing the strawberry extract was most effective in countering the effects of irradiation of the hippocampal task; the diet containing the blueberry extract was most effective in countering the effects of irradiation of the striatal task. These results suggest that the effectiveness of antioxidant diets in countering the neurobehavioral effects of exposure to 56Fe particles may be an interactive effect of the specific diets and endpoints. The results also suggest that a dietary “cocktail” may be necessary to provide the maximum protection against radiation. These findings have important implications for aging, since a similar berry cocktail may be important in forestalling or reversing the deleterious effects of aging. Additional details of this research can be found in the report for the parent CRIS 1950-51000-063-00D Nutritional Modulation of Brain Aging and Cognitive Decline.