Dynorphin A-(1-13) potently improves scopolamine-induced impairment of passive avoidance response in mice.

The effects of intracerebroventricular administration of dynorphin A-(1-13) on scopolamine-induced amnesia were investigated in mice by using a step-down type passive avoidance task. The pre- or post-training, or pre-retention administration of dynorphin A-(1-13)(0.3-10 micrograms) alone failed to affect step-down latency of the passive avoidance response, while scopolamine (1 mg/kg) significantly shortened step-down latency. Dynorphin A-(1-13)(1 microgram) given 15 min before training and retention tests but not immediately after training significantly improved the scopolamine (1 mg/kg)-induced shortening of step-down latency of the passive avoidance response, indicating antiamnesic effects of dynorphin A-(1-13) (1 microgram). A lower dose (1 mg/kg) of the kappa-opioid receptor antagonist, (-)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)- 2'-hydroxy-6,7-benzomorphan, reversed the anti-amnesic effects of dynorphin A-(1-13) (1 microgram). These results suggest that the antiamnesic effects of dynorphin A-(1-13) depend on the timing of drug treatments.