# Effect of the Gestational Fluoxetine Administration on Behavioral Tests and Hippocampal Structure in Male Offspring of Rats

**Authors:** Marcelo Gustavo Lopes, Gabriel Boer Grigoletti-Lima, Patrícia Aline Boer, José Antonio Rocha Gontijo

PMC · DOI: 10.3390/ijms262110758 · International Journal of Molecular Sciences · 2025-11-05

## TL;DR

This study examines how fluoxetine exposure during pregnancy affects rat offspring's behavior and brain structure, finding links to memory and hyperactivity.

## Contribution

The study links gestational fluoxetine exposure to increased hippocampal neuron density and behavioral changes in offspring rats.

## Key findings

- Maternal fluoxetine exposure led to increased hippocampal neuron density in offspring.
- Fluoxetine-treated dams showed reduced parental care, resulting in offspring with increased activity levels.
- Offspring exhibited impaired learning and memory retention but no significant anxiety-like behavior changes.

## Abstract

Depression is a common mental disorder during gestation, posing potential risks to fetal development and leading to behavioral and psychiatric alterations in offspring. Pharmacological intervention, particularly with selective serotonin reuptake inhibitors (SSRIs), is often necessary. This study investigated the effects of fluoxetine (F) on behavioral and memory changes in rodent offspring following maternal gestational and lactation treatment, as well as potential alterations in hippocampal cellularity compared to control (C) progeny. Methodologies included the Morris water maze, elevated plus maze, activity monitoring, parental behavior assessments, and isotropic fractionation for the quantification of hippocampal cells and neurons. Results indicated that maternal fluoxetine exposure significantly affected the body mass, brain weight, and hippocampal metrics of the offspring, aligning with the ‘selfish brain’ hypothesis. Notably, dams treated with fluoxetine showed reduced parental care, leading to offspring with increased activity levels but no changes in anxiety-like behaviors. However, while there was a decline in learning and memory retention, as assessed by the Morris water maze, working and reference memory did not differ significantly from those of controls. This study establishes an association between fluoxetine treatment, increased hippocampal neuron density, and behavioral changes related to memory and hyperactivity, with implications for understanding behavioral disorders and informing future therapeutic interventions.

## Linked entities

- **Chemicals:** fluoxetine (PubChem CID 3386)
- **Diseases:** depression (MONDO:0002050)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Diseases:** anxiety (MESH:D001007), behavioral disorders (MESH:D001523), hyperactivity (MESH:D006948), Depression (MESH:D003866)
- **Chemicals:** Fluoxetine (MESH:D005473)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12608040/full.md

## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC12608040/full.md

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Source: https://tomesphere.com/paper/PMC12608040