Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine

Junichi Kitanaka, Nobue Kitanaka, F. Scott Hall, Mei Fujii, Akiko Goto, Yusuke Kanda, Akira Koizumi, Hirotoshi Kuroiwa, Satoko Mibayashi, Yumi Muranishi, Soichiro Otaki, Minako Sumikawa, Koh Ichi Tanaka, Nobuyoshi Nishiyama, George R. Uhl, Motohiko Takemura

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 b-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 m-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.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalJournal of Experimental Neuroscience
Issue number1
StatePublished - 2015
Externally publishedYes


  • Morphine
  • Morris water maze
  • Spatial memory
  • Y-maze task
  • μ-opioid receptor

ASJC Scopus subject areas

  • Neuroscience(all)


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