Dynorphin A-(1-13) markedly improves scopolamine-induced impairment of spontaneous alternation performance in mice.

The effect of intracerebroventricular (i.c.v.) injection of dynorphin A-(1-13) on the memory process was examined in mice, using spontaneous alternation performance related to working memory in a Y-maze. Dynorphin A-(1-13) (1, 3 and 10 micrograms) influenced neither spontaneous alternation performance nor total arm entries, which are considered to reflect locomotor activity. In contrast, dynorphin A-(1-13) (3 and 10 micrograms) significantly improved the impairment of spontaneously alternation performance induced by scopolamine (1 mg/kg s.c.). Simultaneously, the scopolamine-induced increase in total arm entries was markedly attenuated by dynorphin A-(1-13) (10 micrograms). The effect of dynorphin A-(1-13) (3 micrograms) on the scopolamine-induced impairment of spontaneous alternation was almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms i.c.v.), a kappa-selective opioid antagonist. These findings suggest that dynorphin A-(1-13) improves through the mediation of kappa-opioid receptors the scopolamine-induced impairment of spontaneous alternation performance associated with working memory.