Effects of chronic fluoxetine in animal models of anxiety and depression

Neuropsychopharmacology. 2004 Jul;29(7):1321-30. doi: 10.1038/sj.npp.1300433.


The onset of the therapeutic response to antidepressant treatment exhibits a characteristic delay. Animal models sensitive to chronic, but not acute, antidepressant treatment are greatly needed for studying antidepressant mechanisms. We initially assessed four inbred mouse strains for their behavioral response to chronic treatment with the selective-serotonin reuptake inhibitor fluoxetine (0, 5, 10 mg/kg/day in drinking water), which is used for the treatment of mood and anxiety disorders. Only the highly anxious BALB/c strain exhibited sensitivity to fluoxetine in the forced swim test. Additionally, fluoxetine reduced locomotion in C57BL/6 and 129SvEv, but not BALB/c and DBA/2, strains. We then evaluated the effects of subchronic (approximately 4 days) and chronic (approximately 24 days) fluoxetine treatment (0, 10, 18, 25 mg/kg/day) on measures of anxiety and depression in BALB/c mice. Anxiety measures were obtained using the open field and novelty-induced hypophagia tests. Antidepressant effects were evaluated using the forced swim test. We found 18 mg/kg/day of chronic fluoxetine to be active in all three paradigms; subchronic treatment had no effect. Anxiety-related measures were reduced by 18 mg/kg/day. In the forced swim test, 10 and 18 mg/kg/day increased swimming and reduced immobility. Here we present several novel effects of chronic, but not subchronic, antidepressant treatment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anxiety / blood
  • Anxiety / drug therapy*
  • Behavior, Animal
  • Depression / blood
  • Depression / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Exploratory Behavior / drug effects
  • Fluoxetine / blood
  • Fluoxetine / therapeutic use*
  • Immobilization
  • Male
  • Mice
  • Mice, Inbred Strains
  • Motor Activity / drug effects
  • Reaction Time / drug effects
  • Selective Serotonin Reuptake Inhibitors / blood
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Species Specificity
  • Swimming
  • Time Factors


  • Serotonin Uptake Inhibitors
  • Fluoxetine