Antidepressant-like effects of rosiglitazone, a PPARγ agonist, in the rat forced swim and mouse tail suspension tests

Behav Pharmacol. 2009 Oct;20(7):635-42. doi: 10.1097/FBP.0b013e328331b9bf.


Several studies have evaluated thiazolidinedione therapy as medical treatments for some central nervous system disorders, such as cognitive deficits associated with neurodegenerative disorders. However, there is limited data to support a direct role for peroxisome proliferator-activated receptor-γ agonists in depression. Therefore, the aim of this study was to investigate antidepressant-like activity of rosiglitazone using the mouse tail suspension test and the rat forced swimming test, two models sensitive to the effects of antidepressants. In the tail suspension test, 5 days of treatment with rosiglitazone (8.5 or 17 mg/kg, orally) reduced immobility time. In the forced swimming test, rosiglitazone (6 or 12 mg/kg, orally) treatment decreased immobility time and increased climbing. These effects were not accompanied by any alteration in locomotor activity in the open field test. Rosiglitazone treatment (6 or 12 mg/kg, orally) significantly reduced plasma corticosterone levels in rats. GW9662 significantly inhibited the rosiglitazone-induced reduction in the duration of immobility. In summary, this study suggests that rosiglitazone possesses a specific antidepressant-like activity in behavioral models and that this effect may be mediated by reduction of plasma corticosterone level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology
  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Corticosterone / blood
  • Depressive Disorder / drug therapy*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Immobility Response, Tonic / drug effects*
  • Male
  • Mice
  • Motor Activity / drug effects
  • PPAR gamma / agonists*
  • PPAR gamma / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Rosiglitazone
  • Swimming*
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*


  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Antidepressive Agents
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Corticosterone