Chronic fluoxetine treatment has antidepressant effect in female but not in male mice behavior in forced swim test

Jasmina Kerčmar¹, Stuart A. Tobet², Gregor Majdič¹³
¹Center for Animal Genomics, Veterinary Faculty, University of Ljubljana, Slovenia
²Department of Biomedical Sciences, Colorado State University, Fort Collins, USA
³Institute of Physiology, Medical School, University of Maribor, Slovenia

Numerous studies have reported gender differences in the prevalence of major depressive disorder in humans. Most previous studies have been done in men and in male rodents, but there are fewer behavioral observation studies investigating effects of the antidepressant selective serotonin reuptake inhibitors (SSRIs) in female rats and even less in female mice. It is known that fluoxetine and other SSRIs decrease immobility time in the forced swim test (FST) and increase active swimming time in male rats (antidepressant effect).

In the present study we examined sex differences in FST in mice treated chronically with fluoxetine. The C57BL/6J mice were divided into four socially housed groups: control males and females, treated males and females. Treatment length was at least 14 days with 10mg/kg/day of fluoxetine in drinking water prior to behavioral assessment that involved elevated plus maze, open field test, social recognition test and FST. Only females in diestrus were tested to avoid possible differences in behavior due to hormonal effects. Fluoxetine did not have major impact on any of the behavioral measures evaluated in the mice tested, although there was indication of difference in FST in response to fluoxetine treatment between males and females, and this difference in mice differ from previous studies in rats. Therefore species and sex have to be taken in to account when assessing the effects of anti-depressants.

Keywords: mice, behavior, sex difference, SSRI, fluoxetine