ABSTRACT Recent findings from this laboratory indicate that increases in blood glucose levels can enhance the formation of new memories in rodents and humans. Preliminary findings indicate that glucose effects on the brain appear to interact with central nervous system neurotransmitter actions. In particular, glucose effects are somewhat analogous to those of brain acetylcholine agonists and opiate antagonists. This research project examines the pharmacological bases by which modest increases in circulating glucose levels alter memory and other brain functions. One set of experiments will attempt to demonstrate that direct brain injections of small amounts of glucose have effects on the brain similar to those observed after increases of blood glucose levels. Such findings would support the view that behavioral effects of increases in circulating glucose levels reflect direct glucose actions on the central nervous system. A second set of experiments will compare glucose effects with those of opiate antagonists, to explore the analogous actions of these treatments. Further experiments will examine the interactions of glucose with specific central acetylcholine systems to begin identification of anatomical loci of glucose actions on the brain. Together, the experiments in this project will provide additional characterization of the mechanisms by which relatively small changes in blood glucose levels regulate the functions of the brain.