The effect of fluoxetine on anxiety-related behaviours during development

Selective serotonin reuptake inhibitors (SSRIs) are amongst the most commonly prescribed medications, and there is substantial evidence that they ameliorate symptoms of anxiety and depression. However, much of this research has been conducted in adults, and comparatively little is known about their risks and effectiveness at other ages. The experiments reported in this thesis contribute to addressing this knowledge gap by examining the effects of developmental exposure to fluoxetine (i.e., Prozac), which is one of the most frequently prescribed SSRIs, using a rat model. A significant number of infants are exposed to this drug during gestation or in the early postnatal period as up to 10% of mothers are prescribed SSRIs perinatally, and previous studies show that these drugs cross the placental barrier and are found in breast milk. The experiments described in Chapter 2 failed to find any consistent effects of early-life exposure to fluoxetine on the development of learned fear. Another set of experiments focused on adolescence, which is a peak period for the development of anxiety disorders. Critically, previous research has shown that adolescents are impaired at extinction, which forms the basis of exposure therapy, the gold-standard treatment for aberrant fear and worry. The experiments reported in Chapter 3 show that while fluoxetine improves extinction retention and reduces relapse in adult animals it does not have either effect in adolescents. The experiments reported in Chapter 4 further investigate this difference between adolescents and adults treated with fluoxetine by testing whether a similar pattern occurs on a context conditioning task. Again, the results supported a developmental dissociation in fluoxetine’s effects with it reducing context conditioning in adults but not adolescents. These experiments contribute to elucidating the consequences of fluoxetine treatment during different stages of development. Ultimately experiments such as these allow doctors and patients to more adequately weigh the risks of treatment against the potential benefits, which they cannot currently do because of the relative paucity of research in this area