title: Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol.
abstract: OBJECTIVE
  The intravenous anesthetic propofol caused episodic memory impairments in human. We hypothesized propofol caused episodic-like spatial memory retention but not acquisition impairments in rats and rescuing cAMP response element-binding protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects.
  
  
  METHODS
  Male Sprague-Dawley rats were randomized into four groups: control; propofol (25 mg/kg, intraperitoneal); rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h after propofol injection. Visible MWM training was simultaneously performed to resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min, and 24 h after propofol administration.
  
  
  RESULTS
  Rolipram did not change propofol-induced anesthetic/sedative states or impair motor skills. No difference was found on the latency to the platform during the visible MWM. Propofol impaired spatial memory retention but not acquisition. Rolipram reversed propofol-induced spatial memory impairments and suppression on cAMP levels, CaMKIIα and CREB phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein expression.
  
  
  CONCLUSIONS
  Propofol caused spatial memory retention impairments but not acquisition inability possibly by inhibiting CREB signaling.
authors.affiliation: Department of Anesthesiology and Neuroscience Research Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Shao-Bo
authors.initials: SB
authors.lastname: Zhang
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Xing-Ying
authors.initials: XY
authors.lastname: He
authors.forename: Zui
authors.initials: Z
authors.lastname: Zou
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Sun
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: You
authors.forename: Xue-Yin
authors.initials: XY
authors.lastname: Shi
mesh_terms: D018686:Anesthetics, Intravenous; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003463:Cues; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D006993:Hypnotics and Sedatives; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D004856:Postural Balance / Q000187:drug effects; D015742:Propofol; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*
chemical_list: D018686:Anesthetics, Intravenous; D017362:Cyclic AMP Response Element-Binding Protein; D006993:Hypnotics and Sedatives; D010726:Phosphodiesterase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020889:Rolipram; D015742:Propofol
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