β-lactolin, a whey-derived glycine-threonine-tryptophan-tyrosine lactotetrapeptide, improves prefrontal cortex-associated reversal learning in mice.

Dementia and cognitive decline have become worldwide public health problems. We have previously reported that a whey-derived glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improves hippocampus-dependent memory functions in mice. The supplementation with a whey digest rich in β-lactolin improves memory retrieval and executive function in a clinical trial, but the effect of β-lactolin on prefrontal cortex (PFC)-associated cognitive function was unclear. Here we examined the effect of β-lactolin and the whey digest on PFC-associated visual discrimination (VD) and reversal discrimination (RD) learning, using a rodent touch panel-based operant system. β-Lactolin and the whey digest significantly improved the RD learning, and the whey digest enhanced the response latency during the VD task, indicating that β-lactolin and the whey digest improve PFC-associated cognitive functions. Given the translational advantages of the touch panel operant system, consumption of β-lactolin in daily life could be beneficial for improving human PFC-associated cognitive function, helping to prevent dementia.