Sex-specific behavioral effects of fluoxetine treatment in animal models of depression and anxiety

Jasmina Kerčmar, Gregor Majdič


There are strong sex differences in clinical characteristics and in responses to treatment of several psychiatric diseases. Depressive and anxiety disorders are 2 to almost 3 times more common in women, but the majority of experiments examining the biological basis of these disorders and pharmacological agents for treatments are conducted in male animals. Several studies suggest that females respond better than males to the action of selective serotonin reuptake inhibitors (SSRIs), suggesting that gonadal hormones modulate mood and the response to these drugs. The beginning of clinical use of SSRI fluoxetine (Prozac) in late 80-ies was the frst major breakthrough in the treatment of depression since the introduction of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) nearly 30 years earlier. Fluoxetine is today widely prescribed for the treatment not only of depression but also of some anxiety related disorders. Animal models of depression and anxiety represents a useful tool for the investigation of sex differences of pharmacokinetics and pharmacodynamics of antidepressants. In this review the animal models of depression/anxiety using three most common performed acute stressor behavior tests (forced swim test – FST, elevated plus maze – EPM and open field – OF) will be introduced, followed by presenting behavior alterations after fluoxetine treatment in male and female rodents. In addition, data from our lab in C57BL/6J mice of both sexes on the behavioral effects of chronic fluoxetine treatment in comparison to other studies will be presented. Given the overlap between human and rodent findings, rodents provide a good model for further research on the sex-dependent effects of SSRIs and other antidepressants.

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