Effects of Repeated SSRI Treatment on BDNF and TrkB Receptors in Adolescent Rats

The SSRI antidepressant fluoxetine is one of the few drugs that is both effective at treating depression in adolescent humans and does not markedly increase suicidal ideation. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. Thus, the goal of the present project is to further explore the differences between paroxetine and fluoxetine on the BDNF system in male and female adolescent rats. We will measure the levels of BDNF and the TrkB receptor after 24 h or 14 days after repeated (10 day) or chronic (30 day) exposure to paroxetine (2.5 or 10 g/kg), fluoxetine (10 mg/kg), and vehicle. Twenty-four hours or 14 days after the last drug injection, rats will be rapidly decapitated and their prefrontal cortex and hippocampus is removed. These tissue samples will be used to quantify BDNF, TrkB, and serotonin levels. We expect the BDNF and TrkB levels to be lower in rats treated with paroxetine but not fluoxetine. We also expect the serotonin utilization (ratio of serotonin to the major serotonin metabolite, 5HIAA to be higher in fluoxetine than in paroxetine. Our findings would confirm the neurobiological basis of the differential action of SSRIs on the adolescent brain and the relevant implication in suicidal ideation and behaviors