title: Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine.
abstract: In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or β-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by μ-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety.
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitanaka
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Nobue
authors.initials: N
authors.lastname: Kitanaka
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Mei
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Goto
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Koizumi
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kuroiwa
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Mibayashi
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Muranishi
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Otaki
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Sumikawa
authors.affiliation: Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan.
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan. ; The Office of the Dean, School of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, Baltimore, MD, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Takemura
keywords: Morris water maze; Y-maze task; morphine; spatial memory; μ-opioid receptor