title: Dynorphin A-(1-13) potently improves the impairment of spontaneous alternation performance induced by the mu-selective opioid receptor agonist DAMGO in mice.
abstract: The effects of i.c.v. injection of the mu-selective opioid receptor agonist DAMGO and the effects of its combination with the endogenous kappa-opioid receptor agonist dynorphin A-(1-13) on memory processes were examined in mice, using spontaneous alternation performance associated with working memory in a Y-maze. DAMGO (10 and/or 30 ng) impaired spontaneous alternation performance and increased total arm entries, which are considered to reflect locomotor activity. beta-Funaltrexamine (5 micrograms, i.c.v.), a mu-selective opioid receptor antagonist, almost completely antagonized the impairment of alternation performance induced by DAMGO (10 ng). Physostigmine (0.1 mg/kg, i.p.), a cholinesterase inhibitor, improved the DAMGO (10 ng)-induced impairment of alternation performance. Dynorphin A-(1-13) (1, 3 and 10 micrograms, i.c.v.) alone was without significant effects on alternation performance. On the other hand, dynorphin A-(1-13) (3 and 10 micrograms) significantly improved the impairment of spontaneous alternation performance induced by DAMGO (10 ng). The effects of dynorphin A-(1-13) (3 micrograms) on the DAMGO-induced impairment of spontaneous alternation were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-selective opioid receptor antagonist. The present results demonstrate that DAMGO impairs alternation performance by activating mu-opioid receptors, whereas dynorphin A-(1-13) attenuates the DAMGO-induced impairment of alternation performance through the mediation of kappa-opioid receptors. These findings suggest that mu- and kappa-opioid systems are fully involved in memory function and have opposite effects on spontaneous alternation performance as it is reflected by working memory in mice.
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Itoh
authors.forename: M
authors.initials: M
authors.lastname: Ukai
authors.forename: T
authors.initials: T
authors.lastname: Kameyama
mesh_terms: D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology
chemical_list: D000700:Analgesics; D004745:Enkephalins; D010446:Peptide Fragments; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C026843:dynorphin (1-13); D004399:Dynorphins; D010830:Physostigmine