title: Apoptotic neurodegeneration and spatial memory are not affected by sedative and anaesthetics doses of ketamine/medetomidine combinations in adult mice.
abstract: BACKGROUND
  Ketamine is increasingly popular in clinical practice and its combination with α(2)-agonists can provide good anaesthetic stability. Little is known about the effects of this combination in the brain. Therefore, we investigated the effects of different concentrations of ketamine combined with medetomidine on cognition and its potential apoptotic neurodegenerative effect in adult mice.
  
  
  METHODS
  Seventy-eight C57BL/6 adult mice were divided into six different groups (saline solution, 1 mg kg(-1) medetomidine, 25 mg kg(-1) ketamine+1 mg kg(-1) medetomidine, 75 mg kg(-1) ketamine+1 mg kg(-1) medetomidine, 25 mg kg(-1) ketamine, and 75 mg kg(-1) ketamine). Eight animals per group were tested in the T-maze, vertical pole, and open-field test. Five animals per group were used for histopathological [haematoxylin and eosin (HE) staining] and immunohistochemical analyses [caspase-3 activation and expression of neurotrophin brain-derived neurotrophic factor (BDNF)]. Cells showing clear HE staining and positive immunoreactions for caspase-3 and BDNF in the retrosplenial cortex, visual cortex, pyramidal cell layer of the cornu Ammonis 1 and cornu Ammonis 3 areas of the hippocampus, and in the granular layer of the dentate gyrus were counted.
  
  
  RESULTS
  There were no differences between groups regarding the number of dead cells and cells showing positive immunoreactions in the different areas of the brain studied. Similarly, no differences were detected in the number of trials to complete the T-maze task. Nevertheless, α(2)-agonist decreased hyperlocomotion caused by ketamine in the open field.
  
  
  CONCLUSIONS
  Neither apoptotic neurodegeneration nor alterations in spatial memory were observed with different concentrations of ketamine combined with medetomidine in adult mice.
authors.affiliation: Laboratory Animal Science, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. pribeiro@ibmc.up.pt
authors.forename: P O
authors.initials: PO
authors.lastname: Ribeiro
authors.forename: A M
authors.initials: AM
authors.lastname: Valentim
authors.forename: P
authors.initials: P
authors.lastname: Rodrigues
authors.forename: I A
authors.initials: IA
authors.lastname: Olsson
authors.forename: L M
authors.initials: LM
authors.lastname: Antunes
mesh_terms: D019162:Anesthetics, Combined / Q000008:administration & dosage / Q000633:toxicity; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000633:toxicity*; D007649:Ketamine / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D020926:Medetomidine / Q000008:administration & dosage / Q000633:toxicity*; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000473:pathology; D010100:Oxygen / Q000097:blood
chemical_list: D019162:Anesthetics, Combined; D000778:Anesthetics, Dissociative; D006993:Hypnotics and Sedatives; D007649:Ketamine; D020926:Medetomidine; D010100:Oxygen