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bioRxiv · 10.64898/2026.03.13.711456

Fluoxetine for Prenatal Alcohol-Exposed Mice: Addressing Impaired Enrichment-Mediated Neurogenesis

Rodriguez, A.·Bauer, K.·Tunc-Ozcan, E.·Cunningham, L. A.
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Abstract

BackgroundFetal alcohol spectrum disorder (FASD) encompasses a variety of disorders that occur after a fetus has been exposed to alcohol. Hippocampal related issues are a common neurological deficit found in FASD. The dentate gyrus within the hippocampus is a unique area of the brain that continues to generate new neurons into adulthood. This neurogenesis can be enhanced by an enriched environment (EE); however in prenatal alcohol exposed (PAE) mice this EE-mediated neurogenesis is impaired. In addition to EE, selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, also promote neurogenesis. Here we examine if fluoxetine restores the impaired EE-mediated neurogenesis of PAE mice. MethodPAE mice were generated using a voluntary limited access model where mice received a 10% ethanol (w/v) solution during gestation. To evaluate neurogenesis, we use a NestinCreT2:tdTomato transgenic mouse line in which newborn dentate granule cells (nDGCs) can be evaluated by tdTomato flourescence. PAE and saccharine control (SAC) mice were placed in either standard housing (SH) or enriched environment (EE). Subsequently, we administered fluoxetine (FLX) or vehicle (VEH) after which neurogenesis was evaluated. ResultsPAE resulted in impaired EE-mediated neurogenesis. This neurogenic impairment was not restored by FLX. Interestingly, FLX did increase neurogenesis in PAE mice while housed in SH. ConclusionThese results suggest that there is a neurogenic ceiling in PAE mice that cannot be increased by fluoxetine in EE. However, fluoxetine can increase neurogenesis while the environment is less complex.

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Rodriguez, A., Bauer, K., Tunc-Ozcan, E., Cunningham, L. A.. 2026-03-17. Fluoxetine for Prenatal Alcohol-Exposed Mice: Addressing Impaired Enrichment-Mediated Neurogenesis. https://doi.org/10.64898/2026.03.13.711456

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