Effects of dynorphin A-(1-13) on carbon monoxide-induced delayed amnesia in mice studied in a step-down type passive avoidance task.

The effects of dynorphin A-(1-13) on carbon monoxide (CO)-induced amnesia in mice were investigated using a step-down type passive avoidance task. Memory deficiency occurred in mice when training commenced 7 days after CO exposure although it was not produced 1 day after CO exposure. The median step-down latency in the retention test of the CO-exposed group was significantly shorter than that of the control group. Administration of dynorphin A-(1-13) (1.5 nmol/mouse i.c.v.) 15 min before the first training session prolonged the step-down latency in the CO-exposed group. Dynorphin A-(1-13) administered immediately after the first training session or administered 15 min before the retention test also prolonged the step-down latency in the CO-exposed group. To determine whether this effect of dynorphin A-(1-13) was mediated via kappa-opioid receptors, we attempted to block its action using a kappa-opioid receptor antagonist (nor-binaltorphimine). Nor-binaltorphimine (5.44 nmol/mouse i.c.v.) blocked the effect of dynorphin A-(1-13) on delayed amnesia. However, dynorphin A-(1-13) (0.5, 1.5 and 5.0 nmol/mouse) did not facilitate the acquisition of memory in normal mice. These results suggest that dynorphin A-(1-13) modulates the kappa-opioid receptor-mediated opioid neuronal system, and that it ameliorates the disruptive effect of CO on acquisition, consolidation and/or recall of memory.