The Lacto-Tetrapeptide Gly-Thr-Trp-Tyr, ?-Lactolin, Improves Spatial Memory Functions via Dopamine Release and D1 Receptor Activation in the Hippocampus.

ABSTRACT: SCOPE:Peptides containing tryptophan-tyrosine sequences, including the lacto-tetrapeptide glycine-threonine-tryptophan-tyrosine (GTWY) and ?-lactolin, from ?-lactoglobulin in whey enzymatic digestion, enhance hippocampus-dependent memory functions, which are blocked by the systemic administration of dopamine D1-like antagonist. In this study, we investigated the role of the hippocampal dopaminergic system in the memory-enhancing effect of ?-lactolin. METHODS AND RESULTS:The results of in vivo microdialysis revealed that oral administration of ?-lactolin increased the extracellular concentration of dopamine in the hippocampus and enhanced both spatial working memory, as measured in the Y-maze test, and spatial reference memory, as measured in the novel object location test. These memory-enhancing effects of ?-lactolin, but not the baseline memory functions, were impaired by the knockdown of the dopamine D1 receptor subtype in the hippocampus. ?-Lactolin also enhanced object memory, as measured by the novel object recognition test. However, D1 knockdown in the hippocampus spared this memory function either with or without the administration of ?-lactolin. CONCLUSIONS:The present results indicate that oral administration of ?-lactolin increases dopamine release and D1 receptor signaling in the hippocampus, thereby enhancing spatial memory, but it may improve object memory via a separate mechanism.

SUBMITTER: Ayabe T 

PROVIDER: S-EPMC6835598 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature