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.
Ukai
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Mori
K
K
Hashimoto
S
S
Kobayashi
T
T
Sasaki
Y
Y
Kameyama
T
T
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010147:Pain Measurement; D012153:Retention, Psychology / Q000187:drug effects*
D000701:Analgesics, Opioid; D009842:Oligopeptides; C059394:tyrosyl-arginyl-phenylalanyl-alanine