Adolescent Fluoxetine Exposure Increases ERK-related Signaling Within the Prefrontal Cortex of Adult Male Sprague-Dawley Rats.

Abstract There has been a disproportionate increase in fluoxetine (FLX) prescription rates within the juvenile population. Thus, we evaluated how adolescent FLX exposure alters expression/phosphorylation of proteins from the extracellular signal-regulated kinase (ERK)-1/2 cascade within the adult prefrontal cortex (PFC). Male Sprague-Dawley rats were exposed to FLX (20 mg/kg) for 15 consecutive days [postnatal day (PD) 35–49]. At PD70 (adulthood), we examined protein markers for ERK1/2, ribosomal S6 kinase (RSK) and mammalian target of rapamycin (mTOR). FLX-pretreatment decreased body weight, while increasing PFC phosphorylation of ERK1/2 and RSK, as well as total mTOR protein expression in adulthood. We provide first-line evidence that juvenile FLX pretreatment induces long-term decreases in body weight gain, along with neurobiological changes in the adult PFC—highlighting that early life antidepressant exposure increases ERK-related signaling markers in later life.