Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog, impairs memory consolidation in mice.

Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog with high selectivity and affinity for mu-opioid receptors, was administered intracerebroventricularly to mice before or immediately after training in a one-trial step-down type passive avoidance task. The pre- and post-training administration of TAPA (0.3 and/or 3 ng) impaired retention performance 24 h after training. In particular, the post-training administration of TAPA was much more effective because a lower dose (0.3 ng) of TAPA exclusively inhibited retention performance. The amnesic effects of TAPA were reversed by the mu-selective opioid antagonist beta-funaltrexamine (5 micrograms, i.c.v.). In addition, TAPA (0.3 and 3 ng) had no effects on nociceptive responses in a tail-flick test or on behavioral responses to electric shock during training. These results suggest that activation of mu-opioid receptors impairs passive avoidance learning, resulting in a dysfunction of memory consolidation, without affecting other behavioral responses.