Presentation Title

Effect of Repeated SSRI Exposure on BDNF and TrkB Levels in Adolescent Rats

Start Date

November 2016

End Date

November 2016

Location

Surge 171

Type of Presentation

Oral Talk

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for major depressive disorder because of their low side-­effect profiles and high patient compliance. Unfortunately, the use of SSRIs in adolescent populations is limited due to reduced efficacy and their tendency to induce suicidal ideation. Recently, we observed that repeated fluoxetine and paroxetine treatment increased anxiety-like behaviors in adolescent rats. These adult-atypical behaviors led us to explore the neurochemical basis of SSRI’s limited efficacy. Hence, the purpose of this study was to determine if brain derived neurotropic factor (BDNF) is implicated in mediating the age-specific effects of SSRI exposure in adolescent rats. Male and female adolescent rats (n=6­7) were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (5 or 10 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 and its receptor, TrkB, expression using western blotting. BDNF expression decreased after fluoxetine (5 and 10 mg/kg) treatment in both sexes. Paroxetine also decreased BDNF levels, but only in male rats and at higher doses (10 mg/kg). In summary, repeated treatment with the SSRIs paroxetine and fluoxetine decreased BDNF expression in adolescent rats. This reduction in BDNF could possibly explain the reduced efficacy of SSRIs during adolescence.

This document is currently not available here.

Share

COinS
 
Nov 12th, 2:30 PM Nov 12th, 2:45 PM

Effect of Repeated SSRI Exposure on BDNF and TrkB Levels in Adolescent Rats

Surge 171

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for major depressive disorder because of their low side-­effect profiles and high patient compliance. Unfortunately, the use of SSRIs in adolescent populations is limited due to reduced efficacy and their tendency to induce suicidal ideation. Recently, we observed that repeated fluoxetine and paroxetine treatment increased anxiety-like behaviors in adolescent rats. These adult-atypical behaviors led us to explore the neurochemical basis of SSRI’s limited efficacy. Hence, the purpose of this study was to determine if brain derived neurotropic factor (BDNF) is implicated in mediating the age-specific effects of SSRI exposure in adolescent rats. Male and female adolescent rats (n=6­7) were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (5 or 10 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 and its receptor, TrkB, expression using western blotting. BDNF expression decreased after fluoxetine (5 and 10 mg/kg) treatment in both sexes. Paroxetine also decreased BDNF levels, but only in male rats and at higher doses (10 mg/kg). In summary, repeated treatment with the SSRIs paroxetine and fluoxetine decreased BDNF expression in adolescent rats. This reduction in BDNF could possibly explain the reduced efficacy of SSRIs during adolescence.