Adolescent fluoxetine exposure as a developmental cause of anxiety-like behavior in adult female mice

BACKGROUND: The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) is a first-line pharmacological treatment for mood-related illnesses in the adolescent population - in which girls exhibit approximately twice the risk of being diagnosed with such disorders. Despite increasing FLX prescription rates in adolescents, the potential for unexpected long-term side effects remains poorly understood. To address this issue, we evaluated whether juvenile FLX exposure alters baseline responses to anxiety-inducing environments in adulthood. METHODS: Adolescent female C57BL/6 mice received FLX (20 mg/kg) for 15 consecutive days (postnatal day [PD] 35-49). Three weeks later, once the mice reached adulthood (PD70), separate groups of mice were evaluated on the novelty suppressed feeding test or the elevated plus maze, two behavioral tasks validated for the assessment of anxiety-related responses. RESULTS: We found that adult female mice with adolescent FLX pre-exposure displayed decreases in body weight and exploratory behavior in the elevated plus maze, along with a longer latency to initiate feeding behavior in the novelty suppressed feeding test, without changes in locomotor activity. CONCLUSION: Our data show that adolescent exposure to FLX results in anxiety-like phenotypes in adulthood, suggesting that early-life SSRI exposure may induce long-term changes in neural circuits regulating affective-related behavior.