Effects of Chronic Fluoxetine in Animal Models of Anxiety and Depression

Abstract

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 (B4 days) and chronic (B24 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 noveltyinduced 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.

Maintenance Treatment with Fluoxetine is Necessary to Sustain Normal Levels of Synaptic Markers in an Experimental Model of Depression: Correlation with Behavioral Response

“…In the present work, we show that when LH animals are chronically treated with FLX for 21 days, as expected from other reports (Dulawa et al, 2004), reversion of depressivelike behavior is observed. We demonstrate that a behaviorally successful treatment with the antidepressant FLX fully reverses the diminution of synaptic proteins induced in the CA3 by exposure to the LH paradigm, an animal model of depression.…”

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

“…However, these results are in agreement with data from other labs that have delivered fluoxetine orally. Dulawa et al (2004) found that 4-day fluoxetine treatment had no effect on either the open field test, a measure of general activity and anxietylike behavior, or the forced swim test (FST), another measure of behavioral despair. Similarly, Caldarone et al (2003) found that 21 days of treatment with the tricyclic antidepressant amitriptylene reduced FST immobility to a greater extent than 4 days of treatment.…”

Resolving the neural circuits of anxiety

“…This burying behavior is quantifiable and sensitive to anxiolytics 45,46 . Hyponeophagia (novelty suppressed feeding) has also been used to assess anxiety-like behavior in rodents; in a novel environment, hungry mice exhibit an increased latency to feed that is sensitive to BZDs and SSRIs 47,48 .…”