Effects of Chronic Fluoxetine and Paroxetine on Anxiety-Like Behavior in Adolescent Rats.

The prevalence of Major Depressive Disorder (MDD) in childhood and adolescence is widespread. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant is currently the only FDA approved antidepressant for pediatric populations suffering with MDD. Paroxetine, a very similar SSRI in regards to composition and method of action has been shown to produce age-dependent effects, specifically in suicidal ideation and behavior among adolescent populations. Research regarding the paradoxical effects of these SSRIs on adolescent behavior, and with paroxetine in particular is limited. Consequently, the aim of the present study was to extend the research on the age-dependent effects of chronic fluoxetine and paroxetine treatment in adolescent male and female rats, specifically in regards to anxiety and depression. Sprague-Dawley rats were administered intraperitoneal injections (IP) of paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5 or 10 mg/kg), or vehicle for 30 days from postnatal day (PD) 30-59. Subsequently, on PD 60, anhedonic and anxiety-like behaviors were assessed using sucrose preference and light/dark box tests. On PD 62, the same rats were tested on the elevated plus maze. It was hypothesized that chronic SSRI treatment would alter sucrose preference, time spent in open arms of the plus maze, and time spent in the light compartment of the light/dark box. The present findings revealed that chronic fluoxetine (10 mg/kg) treatment decreased sucrose preference when compared to vehicle-treated rats (i.e., controls), whereas males ingested more sucrose than females regardless of drug treatment. Interestingly, rats treated with chronic fluoxetine or paroxetine did not show an increase in anxiety-like behaviors tested on the elevated plus maze and light/dark box when compared to control rats. These data suggest that chronic exposure to fluoxetine and paroxetine does not increase anxiety-like behaviors when tested on the light-dark box and elevated plus maze shortly after cessation of treatment. However, when presented with the sucrose preference test, rats given chronic exposure to fluoxetine (10 mg/kg) displayed signs of anhedonia