Attenuation of memory with Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog with high affinity for mu-opioid receptors.
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.
Ukai
M
M
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.
Kobayashi
T
T
Mori
K
K
Shinkai
N
N
Sasaki
Y
Y
Kameyama
T
T
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001667:Binding, Competitive; D004347:Drug Interactions; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C102698:tyrosyl-arginyl-phenylalanyl-beta-alaninamide; C030058:dermorphin; D009271:Naltrexone; C024524:beta-funaltrexamine