Suppressive effect of lactoferrin on behavioral abnormality in the maternally separated rats.

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Lactoferrin (LF) is known as an iron-binding glycoprotein, especially contained in milk. We have shown that intra-duodenally administered bovine-LF (bLF) was absorbed from intestine and transported into blood circulation via receptor mediated system in adult rats. We found that a part of the intestinally absorbed bLF was reached to the brain passing through a blood-brain-barrier or a blood-cerebrospinal-barrier. In this project, we focused a suppressive effect of lactoferrin on the behavioral abnormalities related with maternally-separated stresses in rats.Newborn rats were separated individually from home cage and dam from a postnatal day (PND) 2 to PND 11. On the separating day, the newborn rats were separated for 30 min, 1 h, 2 hr and 5 h. Particular abnormalities in behavioral test (elevated plus-maze test) were observed in the 5 h separated rats. Pre-treatment with bLF (100 mg/kg) injection (ip) suppressed these abnormal behaviors. Interestingly, the strongest effect of bLF was recognized when the bLF was applied to the dam rats before the separation. These effects of bLF was blocked by pre-treatment with naloxone, opioid receptor antagonist, or L-NAME, nitric oxide synthase blocker. bLF also suppressed hypothalamus-pituitary-adrenal axis reaction. Plasma corticosterone elevation induced by foot-shock stress was significantly suppressed by bLF in the adult rats.These results suggest that bLF is one of the natural mediators in the stress reaction, via endogenous opioid system and nitric oxide production.