Analysis of gene expression with cDNA microarrays in rat brain after 7 and 42 days of oral lithium administration

Brain Res Bull. 2002 Jan 15;57(2):205-9. doi: 10.1016/s0361-9230(01)00744-4.


The gene expression profile in rat brain was examined using microarrays in rats fed lithium chloride for 7 days (subacute) or 42 days (chronic). Brain lithium concentrations were 0.39 mM and 0.79 mM (therapeutically relevant), at 7 and 42 days, respectively. Of the 4132 genes represented in the microarrays, 25 genes were downregulated by at least twofold and none was upregulated after 7 days of treatment. Expression of 50 genes was downregulated by at least two-fold at 42 days, without any being upregulated. Lithium treatment for 7 days did not affect at a measurable extent expression of 37 of the 50 genes that were downregulated at 42 days. Genes whose expression was changed at 42 days coded for a number of receptors, protein kinases, transcription and translation factors, markers of energy metabolism, and signal transduction. Thus, chronic lithium at a therapeutically relevant concentration reduced expression of a large number of genes involved in multiple signaling and other pathways, without increasing expression at a comparable extent.

MeSH terms

  • Administration, Oral
  • Animals
  • Brain Chemistry / drug effects*
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects*
  • Lithium Chloride / administration & dosage
  • Lithium Chloride / pharmacology*
  • Male
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Oligonucleotide Array Sequence Analysis*
  • Protein Kinases / biosynthesis
  • Protein Kinases / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred F344
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics


  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Transcription Factors
  • Protein Kinases
  • Lithium Chloride