CONICET | Buscador de Institutos y Recursos Humanos

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has been approved to treat major depressive and obsessive-compulsive disorders in pediatric patients along with some off-label uses. Several concerns were raised when it was determined that Fluoxetine could lead children to suicidal thoughts and behaviors. Although well characterized for adults, little is known about the effect of Fluoxetine on pediatric patients. The aim of this work was to evaluate the effect of early exposure to Fluoxetine on social interaction, stereotypical and exploratory activities, and anxiety. Male and female Wistar rats were daily administrated (sc.) with Fluoxetine (10 mg/kg) or saline between postnatal days (PND) 16-35 and behaviorally evaluated at PND 30-35. Concerning social behavior, Fluoxetine treatment in males dramatically reduced social play behavior measured as the number of pinnings and social preference evaluated in a three-chamber task. On the contrary, Fluoxetine did not modify these behaviors in females. Also, only in male, Fluoxetine treatment increased stereotypical behaviors measured as the number of self-grooming events and enhanced anxiety-like behavior indicated by a reduction in the time spent in the open arms of an elevated plus-maze. Notably, while in males Fluoxetine treatment did not affect exploratory activity, in females it decreased the number of hole-pokings. Regardless of sex, Fluoxetine treatment did not modify locomotor activity and increased serotonin immunoreactivity in the hippocampus These results strongly indicate that pre-puberal rat exposure to Fluoxetine targets social interaction, exploration, stereotypical and anxiety-like behaviors in a sex-dependent manner. Our results also highlight male vulnerability to modulation of serotonin levels during infancy and pre-puberty.