Administration of alpha_s1-casein hydrolysate increases sleep and modulates GABA_A receptor subunit expression

Sleep is the most basic and essential physiological requirement for mental health, and sleep disorders pose potential risks of metabolic and neurodegenerative diseases. Tryptic hydrolysate of α_S1 -casein (α_S1 -CH) has been shown to possess stress relieving and sleep promoting effects. However, the differential effects of α_S1 -CH on electroencephalographic wave patterns and its effects on the protein levels of γ-aminobutyric acid A (GABA_A) receptor subtypes in hypothalamic neurons are not well understood. We found α_S1 -CH (120, 240 mg/kg) increased sleep duration in mice and reduced sleep-wake cycle numbers in rats. While α_S1 -CH (300 mg/kg) increased total sleeping time in rats, it significantly decreased wakefulness. In addition, electroencephalographic theta (θ) power densities were increased whereas alpha (α) power densities were decreased by α_S1 -CH (300 mg/kg) during sleep-wake cycles. Furthermore, protein expressions of GABA_A receptor β₁ subtypes were elevated in rat hypothalamus by α_S1 -CH. These results suggest α_S1 -CH, through GABA_A receptor modulation, might be useful for treating sleep disorders.