Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression

Int J Mol Sci. 2021 Jan 24;22(3):1148. doi: 10.3390/ijms22031148.


Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.

Keywords: animal model; brain; depressive-like behavior; lithium; manic-like behavior; transcriptome.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Antimanic Agents / pharmacology
  • Antimanic Agents / therapeutic use
  • Brain / metabolism*
  • Depression / drug therapy*
  • Depression / genetics
  • Disease Models, Animal
  • Lithium / pharmacology*
  • Lithium / therapeutic use
  • Male
  • Mania / drug therapy*
  • Mania / genetics
  • Rats
  • Rats, Wistar
  • Transcriptome*


  • Antidepressive Agents
  • Antimanic Agents
  • Lithium