Juvenile fluoxetine treatment affects the maturation of the medial prefrontal cortex and behavior of adolescent female rats

Abstract

BackgroundSerotonin is strongly involved in the regulation of brain development. An early-life imbalance in brain serotonin levels may influence the proper formation of neuronal circuits and synaptic plasticity. One of the factors that can affect serotonin concentrations is exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, the first-line pharmacological treatment for depression and anxiety in the pediatric population. Women are more prone to depression and anxiety from a young age. The safety of early-life FLX treatment is still questionable. We hypothesized that juvenile FLX treatment influences the brain maturation and behavior of adolescent females. MethodsOn postnatal days (PNDs) 20-28, juvenile female rats were injected once daily with FLX. Five days later, anxiety- and fear-related behaviors and the response to amphetamine were assessed. On PND 40, the numbers of neurons and glial cells in the medial prefrontal cortex (mPFC) and hippocampus were estimated via stereological methods. Additionally, the mRNA expression of cell survival/apoptosis and synaptic plasticity markers was evaluated via RT-qPCR. ResultsJuvenile FLX attenuated anxiety-like behaviors, impaired fear memory and blunted the locomotor response to amphetamine in adolescent females. Simultaneously, FLX increased the regional volume and the numbers of neurons and astrocytes in specific subregions of the mPFC but not in the hippocampus. Additionally, FLX-treated females presented increased expression of genes regulating cell survival and reduced mRNA levels of AMPA glutamate receptors in the mPFC. ConclusionsJuvenile FLX affects the maturation of the mPFC; therefore, this psychotropic drug should be used with caution in young people.