# Prenatal Stress Induces Changes in Behavior, HPA Axis, Inflammation, and Oxidative Stress in Adult Rats Offspring

## TL;DR

Prenatal stress in rats leads to long-term behavioral and biochemical changes in offspring, which may contribute to psychiatric disorders.

## Contribution

This study demonstrates that prenatal stress induces lasting behavioral and biochemical effects in offspring, partially mitigated by lithium.

## Key findings

- Female offspring from stressed dams showed hyperactivity and altered behavior.
- Prenatal stress increased pro-inflammatory cytokines and oxidative damage markers in offspring brains and serum.
- Lithium administration reduced biochemical alterations caused by prenatal stress.

## Abstract

Prenatal stress is related to the development of psychiatric disorders involving inflammation, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis. Therefore, the aim of the present study was to evaluate the effects of prenatal stress on behavior, inflammation, oxidative stress, and the HPA-axis in the dams and their offspring treated with lithium. Thirteen pregnant Wistar rats were exposed to a prenatal chronic unpredictable stress protocol from the 14th day of gestation until birth. At the 60th postnatal day (PND), a treatment protocol was carried out in the offspring with lithium (intraperitoneally – 47.5 mg/kg) or saline for seven days (twice a day). The behavior was assessed in the open field test to evaluate free movements. The dams (21 PND) and offspring (after open field) were euthanized, their brains were dissected in frontal cortex, hippocampus, and striatum, and the serum was collected. In the brain and/or serum, the levels of oxidative stress, inflammation, and HPA axis parameters were evaluated. Female offspring from stressed dams showed hyperactivity. Besides behavior alterations, offspring brain and serum showed an increase in pro-inflammatory cytokines, oxidative damage markers, and HPA axis hormones levels. Lithium administration only reduced the biochemical alterations. The prenatal stress protocol induced long-lasting behavior, inflammatory, oxidative stress, and HPA-axis alterations in the offspring which could underlie the development of psychiatric disorders.

The online version contains supplementary material available at 10.1007/s11064-026-04672-3.