title: Opioid mediated suppressive effect of milk-derived lactoferrin on distress induced by maternal separation in rat pups.
abstract: The present study assessed the effects of bovine milk-derived lactoferrin (bLf) on distress activities induced by maternal separation in 5- to 18-day-old rat pups. The rat pups were injected with BSA (100 mg/kg, i.p.; control) or bLf (100 mg/kg, i.p.) 30 min before the behavioral test. Distress activity was estimated by means of recording body movements or ultrasonic vocalizations (USVs). After 5 min of maternal separation, bLf significantly (P<0.01) suppressed body movements, particularly in the 10-day-old pups. This suppressive effect of bLf was reversed by pretreatment with naloxone, CTOP, and norBNI at doses of 0.1-1 mg/kg. Additionally, USVs were also suppressed by bLf, which was reversed by pretreatment with naloxone. Inhibition of nitric oxide synthase (NOS) with nitro-L-arginine methyl ester (L-NAME) dose dependently (3-10 mg/kg) suppressed separation-induced USV production in 10-day-old pups. Interestingly, the suppressive effect of bLf was completely reversed by pretreatment with a low dose (1 mg/kg) of L-NAME, which did not affect the USVs with single application. These findings demonstrate that milk-derived bLf suppresses distress induced by maternal separation via an opioid-mediated mechanism. Furthermore, bLf possibly activates NOS, and an elevated nitric oxide may cause some modification of the opioid system.
authors.affiliation: Department of Veterinary Physiology, Faculty of Agriculture, Tottori University, 680-0945, Tottori, Japan. takeuchi@muses.tottori-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Ken ichiro
authors.initials: Ki
authors.lastname: Hayashida
authors.forename: Hideaki
authors.initials: H
authors.lastname: Inagaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kuwahara
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsubone
authors.forename: Etsumori
authors.initials: E
authors.lastname: Harada
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007781:Lactoferrin / Q000494:pharmacology*; D008426:Maternal Deprivation; D008892:Milk / Q000737:chemistry; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011869:Radioligand Assay; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D019001:Nitric Oxide Synthase; D007781:Lactoferrin; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone