title: Suppressive effects of milk-derived lactoferrin on psychological stress in adult rats.
abstract: Lactoferrin (LF) is known as an iron-binding glycoprotein. It has been shown that bovine LF (bLF) is transported into cerebrospinal fluid via blood although its physiological effects in the central nervous system (CNS) are still unclear. In this study, a suppressive effect of bLF on psychological distress was investigated in adult rats. Intraperitoneal injection of bLF (100 mg/kg) reduced stressful behaviors in a conditioned fear-induced freezing test and an elevated plus-maze test. Interestingly, the suppressive effect of bLF was enhanced by pretreatment with electric foot-shock (FS). This suppressive effect of bLF in the elevated plus-maze test was reversed by pretreatment with naloxone, an opioid receptor antagonist, at a dose of 1 mg/kg (ip). N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, also blocked the suppressive effect of bLF and foot-shock. In addition, combined application of a low dose of bLF (30 mg/kg, ip) and l-arginine (30 and 100 mg/kg, ip) showed significant potentiated effects on psychological stress. These results suggest that bLF has suppressive effects on psychological distress, especially under the condition of moderate stress. Furthermore, it is suggested that bLF possibly activates an endogenous opioidergic system via nitric oxide synthase activation.
authors.affiliation: Department of Veterinary Physiology, Faculty of Agriculture, Tottori University, Tottori 680-0945, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Kamemori
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Hayashida
authors.forename: Etsumori
authors.initials: E
authors.lastname: Harada
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001120:Arginine / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007781:Lactoferrin / Q000494:pharmacology* / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011678:Punishment; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D009270:Naloxone; D001120:Arginine; D019001:Nitric Oxide Synthase; D007781:Lactoferrin; D019331:NG-Nitroarginine Methyl Ester