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The involvement of mu-opioid receptors in memory retrieval was examined in mice by using Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog with high affinity for mu-opioid receptors, and passive avoidance learning. TAPA was intracerebroventricularly administered to mice before retention tests of passive avoidance learning. A 0.3-ng dose of TAPA markedly shortened step-down latency of passive avoidance learning, and the shortening of step-down latency was reversed by treatment with beta-funaltrexamine (5 micrograms), a mu-opioid receptor antagonist, indicating that TAPA (0.3 ng) attenuates memory retrieval. Although the attenuating dose (0.3 ng) of TAPA failed to affect horizontal or vertical locomotor activity, a 3-ng dose of TAPA showed a tendency to decrease vertical locomotor activity. A 30-ng dose of TAPA produced a significant increase in horizontal locomotor activity accompanied by a marked reduction of vertical locomotor activity. TAPA (3 ng) produced a significant increase in step-down latency of passive avoidance learning with lower intensity of electroshock or without electroshock during training. These results suggest that the activation of mu-opioid receptors impairs memory retrieval.
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