The purpose of this research is to determine if undernutrition during the neonatal period, at a time several regions of the CNS of mammals (rats) are still going through growth and proliferation, can render experimental subjects more vulnerable to neurotoxic insults later in life. In order to control for environmental factors (e.g. changes in maternal behavior) which inevitably confound nutritional manipulations in neonates, initial research will determine equivalent levels of malnutrition induced by three different procedures: fostering pups to non-lactating dams on several days during the first week of life, varying the number of mammae, or varying the number of pups/litter. Populations as nearly identical as possible with regard to growth curves, brain weights and standard neurochemical parameters (brain DNA, RNA and protein) will than be compared in a test of learning and memory, using a discrete trials, appetitively motivated autoshaping procedure. Other procedures used to assay neurobehavioral functioning will include kindling of convulsions by repeated immersion in heated water, and pituitary adrenal response to stress. Finally, apparently normal rats, malnourished by three procedures as neonates, will be treated with neurotoxins as adults, to determine, using neurobehavioral tests, if they are differentially vulnerable to neurotoxic insult. Toxicants to be used include p-bromephenylacetyl-urea (BPAU) which primarily affects the peripheral nervous system, methyl mecury, a substance which has peupheral effects similar to those produced by BPAU, but which also damages the central nervous system (CNS), and trimethyltin, a substance which primarily affects CNS limbic structures.
