Dynorphin A-(1–13) potently prevents memory dysfunctions induced by transient cerebral ischemia in mice

Abstract

The effect of dynorphin A-(1–13), an endogenous κ-opioid receptor agonist, on memory dysfunctions induced by transient cerebral ischemia in mice was investigated by using three different tasks, namely, spontaneous alteration, elevated plus-maze performance, and passive avoidance behavior. Transient ischemia produced a marked memory dysfunction in mice, as assessed in the three tasks, which were carried out consecutively 1 to 3 days after the ischemic insult. The i.c.v. injection of dynorphin A-(1–13) before the ischemic insult potently prevented the impairment of spontaneous alternations, the prolongation of transfer latency in the elevated plus-maze and the shortening of step-through latency in the passive avoidance task induced by transient ischemia. Dynorphin A-(1–13) (10 μg), however, did not affect the body temperature of the sham-operated or the ischemic mice. The protective effect of dynorphin A-(1–13) (10 μg) on ischemia-induced memory dysfunctions observed in the three tasks was almost completely reversed by pretreatment with nor-binaltorphimine (4 μg, i.c.v.), a κ-selective opioid receptor antagonist. These results suggest that dynorphin A-(1–13) prevents memory dysfunctions in ischemic mice through the activation of κ-opioid receptors.