Effects of systemic administration of β-casomorphin-5 on learning and memory in mice

The effects of systemic administration of bovine β-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), a μ-opioid receptor agonist derived from milk β-casein, on spontaneous alternation behavior in the Y-maze (spatial short-term memory) and step-down-type passive avoidance response (non-spatial long-term memory) were investigated in mice. Intraperitoneal (i.p.) administration of β-casomorphin-5 (0.1–20 mg/kg) did not have a significant effect on either spontaneous alternation behavior or passive avoidance response. However, a low dose (1 mg/kg, i.p.) of β-casomorphin-5 improved scopolamine (1 mg/kg, s.c.)-induced impairment of spontaneous alternation behavior and passive avoidance response. Pretreatment with intracerebroventricular injections of β-funaltrexamine (a μ-opioid receptor antagonist, 0.1 μg/mouse) and naloxonazine (a μ1-opioid antagonist, 5 μg/mouse), which did not improve scopolamine-induced impairment, prevented the ameliorating effect of β-casomorphin-5 on scopolamine-induced impairment of passive avoidance response. These results indicated that systemic administration of a low dose (1 mg/kg, i.p.) of β-casomorphin-5 improves the disturbance of learning and memory resulting from cholinergic dysfunction through central mediation involving μ1-opioid receptors.