Effects of Repeated Paroxetine on Acoustic Startle and Pre-pulse Inhibition in Adolescent Male and Female Rats

RM 216

Depression is a common problem during adolescence, but the most commonly prescribed class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), often lack efficacy and can induce suicidal ideation in adolescents. It is possible that SSRIs, such as paroxetine (PAX), may have anxiogenic (anxiety producing) effects on adolescents. Thus, we assessed the effects of repeated PAX treatment on acoustic startle response (ASR), which is a measure of anxiety. Male and female Sprague-Dawley rats (N=192) were injected with PAX (1.25, 2.5, 5 or 10 mg/kg, IP) or vehicle for 10 consecutive days starting on postnatal day 35, then tested on ASR for 5 days; 1, 7, or 28 days post treatment. PAX had a sex-dependent effect on the body weights of adolescent rats, with male rats losing weight at 10 mg/kg, and females gaining weight at 1.25 mg/kg. The magnitude of the ASR was greater for males on all test days. At each age tested, exposure to PAX (10 mg/kg) increased habituation of the ASR, but only in male rats. Interestingly, there was a marginal interaction between sex and test day when the PPI scores were analyzed. Specifically, male rats showed increased PPI relative to females, with the greatest sex difference occurring 28 days after the last drug treatment. Overall, these data show that adolescent female rats exhibit less anxietylike behavior than males after repeated paroxetine treatment, and these paroxetine-induced effects are still apparent four weeks after the last drug treatment.