Dynorphin A-(1-13) and (2-13) improve beta-amyloid peptide-induced amnesia in mice

The anti-amnesic effects of dynorphins on beta-amyloid peptide-(25-35)-induced impairment of learning and/or memory in mice were investigated using a Y-maze task and a passive avoidance test. Administration of beta-amyloid peptide-(25-35) (betaAP(25-35); 8.2 nmol, i.c.v.) 7 and 14 days before behavioral tests induced a decrease in both alternation behavior and latency in passive avoidance tests. Dynorphin A-(1-13) and A-(2-13) (0.5 and/or 1.5 nmol, i.c.v.) 30 min before behavioral tests improved the beta-amyloid peptide-(25-35)-induced impairment of alternation performance and shortened the step-down latency. Nor-binaltorphimine (4.9 nmol, i.c.v.) partially blocked the effects of dynorphin A-(1-13), but not A-(2-13). These results indicate that dynorphin A-(1-13) and A-(2-13) improve amnesia induced by betaAP-(25-35) via not only kappa opioid receptors, but also by non-opioid mechanisms.