Effects Of Repeated Paroxetine And Fluoxetine Exposure On Hippocampal Bdnf Functioning In Adolescent Rats

RM 218

The use of SSRIs in pediatric populations is limited due to reduced efficacy and their tendency to induce suicidal ideation in adolescents. Recently, we found that repeated treatment with fluoxetine and paroxetine caused increased anxiety-like behaviors in adolescent rats, as measured on the elevated plus maze and light/dark box. The purpose of the present study was to determine if changes in brain derived neurotropic factor (BDNF) functioning are responsible for mediating these age-dependent behavioral and neurochemical effects. The rationale for this study was based on a growing body of evidence suggesting that the therapeutic effects of antidepressants are dependent on BDNF-mediated increases in neurogenesis. To test our hypothesis, we measured the expression of BDNF and the BDNF receptor, after repeated paroxetine and fluoxetine treatment. Male and female adolescent Sprague Dawley rats (n=67) were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (5 or10 mg/kg), or vehicle for 10 consecutive days starting on postnatal day (PD) 35. On PD 45, the hippocampus of each rat was removed and then assayed for BDNF expression using western blotting. In both male and females rats, BDNF expression was decreased after fluoxetine (5 and 10 mg/kg) treatment. Paroxetine (10 mg/kg) also decreased BDNF levels, but only in male rats. Repeated treatment with the SSRIs paroxetine and fluoxetine led to decreased BDNF expression in adolescent rats. This reduction in BDNF levels may be responsible for the reduced efficacy of SSRIs during adolescence. Interestingly, paroxetine had a greater effect on the BDNF functioning of male rats than females.