Gene expression profiling in the developing rat brain exposed to ketamine

Neuroscience. 2010 Mar 31;166(3):852-63. doi: 10.1016/j.neuroscience.2010.01.007. Epub 2010 Jan 18.


Ketamine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with accelerated neuronal apoptosis in the developing rodent brain. In this study, postnatal day (PND) 7 rats were treated with 20 mg/kg ketamine or saline in six successive doses (s.c.) at 2-h intervals. Brain frontal cortical areas were collected 6 h after the last dose and RNA isolated and hybridized to Illumina Rat Ref-12 Expression BeadChips containing 22,226 probes. Many of the differentially expressed genes were associated with cell death or differentiation and receptor activity. Ingenuity Pathway Analysis software identified perturbations in NMDA-type glutamate, GABA and dopamine receptor signaling. Quantitative polymerase chain reaction (Q-PCR) confirmed that NMDA receptor subunits were significantly up-regulated. Up-regulation of NMDA receptor mRNA signaling was further confirmed by in situ hybridization. These observations support our working hypothesis that prolonged ketamine exposure produces up-regulation of NMDA receptors and subsequent over-stimulation of the glutamatergic system by endogenous glutamate, triggering enhanced apoptosis in developing neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, General / toxicity*
  • Animals
  • Animals, Newborn
  • Brain / drug effects*
  • Brain / growth & development
  • Brain / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Profiling*
  • In Situ Hybridization
  • Ketamine / toxicity*
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Rats
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Signal Transduction
  • Terminology as Topic
  • Up-Regulation


  • Anesthetics, General
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine