Milk Collected at Night Induces Sedative and Anxiolytic-Like Effects and Augments Pentobarbital-Induced Sleeping Behavior in Mice

Abstract

Milk has long been known and used to promote sleep. The sleep-promoting effect of milk has been attributed to its psychological associations (i.e., the memory of a mother giving milk at bedtime) and its rich store of sleep-promoting constituents (e.g., tryptophan). Studies have shown that milk harvested at night (Night milk) contains exceptionally high amounts of tryptophan and melatonin. In the present study, we evaluated the psychopharmacological properties of Night milk, particularly its probable sleep-promoting/enhancing, and anxiolytic effects. Night milk was orally administered to ICR mice at various concentrations (100, 200, or 300 mg/kg). An hour after administration, assessment of its sedative (open-field and rotarod tests) and sedative sleep-potentiating effects (pentobarbital-induced sleeping test) was conducted. For comparison, the effects of Day milk (daytime milking) were also assessed. In addition, the effects of Night milk on anxiety behavior (elevated plus maze [EPM] test) and electroencephalographic (EEG) waves were evaluated. Night milk-treated animals exhibited decreased spontaneous locomotion (open-field test) and impaired motor balance and coordination (rotarod test). Furthermore, Night milk shortened the sleep onset and prolonged the sleep duration induced by pentobarbital sodium. These effects were comparable to that of diazepam. In addition, Night milk significantly increased the percentage of time spent and entries into the open arms of the EPM, indicating that it also has anxiolytic effects. No significant changes in EEG waves were observed. Altogether, these findings suggest that Night milk is a promising natural aid for sleep-and anxiety-related disturbances.

Effects of Diet on Sleep Quality

“…To further corroborate the potential sleep-inducing effects of nighttime milk, another study showed that melatonin-enriched milk improved sleep efficiency and reduced the number of awakenings in middleaged adults diagnosed with insomnia (49). Nighttime milk, which is abundant in Trp and melatonin, shortens the onset and prolongs the duration of sleep in mice (50) and has a sedating effect. In mice, motor balance and coordination are reduced to a level comparable to known sedatives with the administration of nighttime milk.…”

“…An analysis of milk content in one study revealed that nighttime milk contained higher amounts of Trp (4.66 mg/g) and melatonin (85.5 pg/g) than daytime milk (3.75 mg/g and 8.8 pg/g, respectively) (50). Another study used nighttime milk with a melatonin concentration of 10.2-18.3 pg/mL, with subjects consuming 0.5 L milk/d (41).…”

Transcriptional profiling of SHR/NCrl prefrontal cortex shows hyperactivity‐associated genes responsive to amphetamine challenge

“…We are currently performing the latter in keeping with our long-standing interest to determine genetic biomarkers of ADHD behaviors (dela Peña et al 2015a(dela Peña et al ,2015b. Identification of these genes was facilitated through selection of common DEGs in the PFC of hyperactive SHR/NCrl vs. WKY/NCrl and Wistar control rats and further validations of the differential expression levels of these genes in drug-naïve SHR/NCrl and also in AMPH-treated SHR/NCrl which showed attenuated locomotor activity.…”

“…these genes in the PFC of control strains thereby increasing their activity may further verify the involvement of these genes in mediating hyperactivity in SHR/NCrl. We are currently performing the latter in keeping with our long-standing interest to determine genetic biomarkers of ADHD behaviors (dela Peña et al 2015a(dela Peña et al ,2015b. Of interest, although outside of the scope of this study, identifying AMPH-regulated genes in the PFC of WKY/NCrl and Wistar rats which showed locomotor sensitization to AMPH may help determine candidate genes that mediate such behavioral effect of AMPH treatment.…”

“…Locomotor activity was evaluated in a square Plexiglas open-field arena measuring 42 × 42 × 42 cm following methods described in our previous studies with minor modification (dela Peña et al, 2013;dela Peña et al 2015adela Peña et al ,2015bBotanas et al 2016). To start an experiment, rats were gently placed in the center of the open-field and allowed to explore the whole arena spontaneously.…”