title: Repeated administration of ketamine may lead to neuronal degeneration in the developing rat brain.
abstract: BACKGROUND
  This study was conducted to investigate, in vivo, the dose and duration effects of ketamine administration on neuronal degeneration in the developing rat brain.
  
  
  METHODS
  Seven-day-old (P7) Sprague-Dawley rats were treated with intraperitoneal injections of ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist. Degenerating neurones were identified by the cupric-silver stain from 10 brain regions using the stereological disector method.
  
  
  RESULTS
  A single dose of ketamine (25, 50 and 75 mg.kg-1) did not increase neuronal degeneration compared with the saline-treated control. However, repeated doses of ketamine (25 mg.kg-1) at 90-min intervals over 9 h increased degenerating neurones in seven out of 10 brain regions.
  
  
  CONCLUSIONS
  These findings suggest that the duration of ketamine exposure correlates with increased neuronal degeneration in the developing rat brain.
authors.affiliation: Department of Anesthesia, Kansai Rosai Hospital, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Pieter
authors.initials: P
authors.lastname: Dikkes
authors.forename: Sulpicio G
authors.initials: SG
authors.lastname: Soriano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine