Effects Of Repeated Paroxetine Exposure On Acoustic Startle In Adolescent Rats

Major depression is a common problem in adolescents, yet many of the medications that are effective at relieving the symptoms of depression in adults are ineffective in adolescent populations. Moreover, the most popular class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), can induce suicidal ideation in adolescents. The mechanism for this paradoxical increase in suicidal ideation is unknown but recent research in our laboratory suggests that paroxetine may increase anxiety in adolescent rats. Therefore, we assessed the effects of repeated paroxetine treatment on acoustic startle response (ASR). Male and female Sprague-Dawley rats (N=192) were injected with paroxetine (1.25, 2.5, 5 or 10 mg/kg, IP) or vehicle for 10 consecutive days starting on postnatal day (PD) 35. Rats were then tested for ASR for 5 days starting 1, 7, or 28 days after the last drug treatment. Paroxetine administration had a differential affect on the weight of adolescent rats by sex. Male rats were more sensitive to ASR than female rats on all test days. However, exposure to paroxetine (10 mg/kg) reduced ASR in both sexes, while treatment with the 1.25 dose of paroxetine decreased the habituation of the ASR for male rats. In this study, paroxetine affected anxiety-like behavior as measured by ASR in a sex- and dose-dependent manner in adolescent rats. Men and women exhibit different rates of depression and our findings suggest that sex and age could be important in determining antidepressant treatment