Fluoxetine enhances the retention of fear extinction in corticosterone-exposed male adolescent rats.

Adolescents have impaired fear regulation, especially after chronic stressor exposure. Treatments that typically improve the retention of fear extinction in adolescent rats are not effective in those exposed to elevated levels of stress-related hormones (e.g., cortisol in humans, corticosterone in rats). Here, we examined whether the negative effects of chronic corticosterone exposure on fear extinction in adolescent rats could be ameliorated by fluoxetine (Prozac), a commonly prescribed selective serotonin reuptake inhibitor (SSRI). We found that chronic stressor exposure, as mimicked by oral corticosterone treatment, impaired fear extinction retention in male adolescent rats (Experiment 1). However, chronic (13 days) or sub-chronic (7 days) treatment with fluoxetine (10 mg/kg) enhanced the retention of fear extinction in corticosterone-exposed adolescents (Experiments 1 and 2). In contrast, vehicle-exposed adolescent rats were unaffected by chronic fluoxetine exposure (Experiment 1). These findings add to the growing evidence that corticosterone exposure alters treatment responses during adolescence and, importantly, suggest that fluoxetine could be an effective treatment for adolescents exposed to high levels of stress-related hormones (at least in male rats).