title: A single intraperitoneal injection of ketamine does not affect spatial working, reference memory or neurodegeneration in adult mice: An animal study.
abstract: BACKGROUND
  Ketamine is an anaesthetic and analgesic drug used in research and clinical practice. Little is known about the effects of different doses of this drug on memory and brain cellular death.
  
  
  OBJECTIVE
  To study the effects of different doses of ketamine on working and reference memory, and neurodegeneration in adult mice.
  
  
  METHODS
  A randomised study.
  
  
  METHODS
  The study was carried out in a basic science laboratory, between March 2011 and August 2012.
  
  
  METHODS
  Forty-eight 7-month-old, male C57BL/6 mice were used.
  
  
  METHODS
  Animals received a single intraperitoneal injection of physiological saline solution or one of three doses of ketamine (25, 75 or 150 mg kg(-1)). Each group consisted of 12 animals (seven animals for behavioural tests and five animals for histopathological and immunohistochemical studies). The animals used for histopathology studies were sacrificed 3 h after anaesthesia.
  
  
  METHODS
  Working and reference memories were assessed using the radial-maze test over 12 consecutive days. The equilibrium was tested using the vertical pole (4 and 24 h after injection), whereas locomotion was assessed using the open field (24, 48 and 72 h after injection). Histopathological (haematoxylin-eosin staining) and immunohistochemical analyses (procaspase-3 and activated caspase-3 detections) were performed 3 h after injection to assess neurodegeneration in the retrosplenial and visual cortices, pyramidal cell layer of the cornu Ammonis 1 and cornu Ammonis 3 areas of the hippocampus, in the granular layer of the dentate gyrus, in the laterodorsal thalamic nucleus, striatum and accumbens nucleus.
  
  
  RESULTS
  No significant differences were observed between the groups regarding the number of dead cells and cells showing positive immune-reactivity in the different regions of the brain studied. The performance in the vertical pole test and the number of reference and working memory errors in the radial-maze were similar in all groups. Nevertheless, the animals treated with ketamine 75 mg kg(-1) were transiently more active, walking a greater total distance at a greater speed in the open field than other groups (power of 0.96).
  
  
  CONCLUSIONS
  These data indicate that a single intraperitoneal injection of ketamine at subanaesthetic and anaesthetic doses does not impair working memory, reference memory or neurodegeneration in adult mice, but an intermediate dose of ketamine produces transitory hyperlocomotion.
authors.affiliation: Laboratory Animal Science, Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal. pribeiro@ibmc.up.pt
authors.forename: Patrícia O
authors.initials: PO
authors.lastname: Ribeiro
authors.forename: Paula C
authors.initials: PC
authors.lastname: Rodrigues
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valentim
authors.forename: Luís M
authors.initials: LM
authors.lastname: Antunes
mesh_terms: D000778:Anesthetics, Dissociative / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration; D065852:Spatial Memory / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine