Scope: Peptides containing tryptophanâ??tyrosine sequences, including the lacto-tetrapeptide\nglycineâ??threonineâ??tryptophanâ??tyrosine (GTWY) and Beta-lactolin, from Beta-lactoglobulin in whey\nenzymatic digestion, enhance hippocampus-dependent memory functions, which are blocked\nby the systemic administration of dopamine D1-like antagonist. In this study, we investigated the\nrole of the hippocampal dopaminergic system in the memory-enhancing effect of Beta-lactolin. Methods\nand Results: The results of in vivo microdialysis revealed that oral administration of Beta-lactolin\nincreased the extracellular concentration of dopamine in the hippocampus and enhanced both spatial\nworking memory, as measured in the Y-maze test, and spatial reference memory, as measured in\nthe novel object location test. These memory-enhancing effects of Beta-lactolin, but not the baseline\nmemory functions, were impaired by the knockdown of the dopamine D1 receptor subtype in the\nhippocampus. Beta-Lactolin also enhanced object memory, as measured by the novel object recognition\ntest. However, D1 knockdown in the hippocampus spared this memory function either with or without\nthe administration of Beta-lactolin. Conclusions: The present results indicate that oral administration\nof Beta-lactolin increases dopamine release and D1 receptor signaling in the hippocampus, thereby\nenhancing spatial memory, but it may improve object memory via a separate mechanism.
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