# The effect of chronic stress and chronic alcohol intake on behaviour, brain volume, and functional connectivity in a longitudinal rat model

## TL;DR

This study shows how chronic stress and alcohol affect brain structure and function differently in male and female rats over time.

## Contribution

The study reveals sex-dependent and region-specific effects of combined chronic stress and ethanol exposure on brain plasticity during neurodevelopment.

## Key findings

- Chronic stress reduced body weight gain and impaired recognition memory in rats.
- Ethanol and stress exposure caused additive brain volume changes in key regions like the hippocampus and cerebellum.
- Functional connectivity disruptions were sex-dependent, with males showing more volumetric changes and females more connectivity changes.

## Abstract

Pathological chronic stress is stress exceeding the organism's ability to cope physiologically, which may act as a risk factor in the onset and relapse of alcohol use disorder. Chronic-restraint stress (CRS) and ethanol intake are independently known to induce changes in brain structure and function, however, their combined effects on neurodevelopment over long periods of time remains largely unexplored. We conducted an in vivo longitudinal rat model with three main goals. 1) to determine if chronic stress increases ethanol intake; 2) to determine the effect of chronic- stress and ethanol intake in behavioural measures, brain structure, and function; and 3) to investigate the effect of sex. This observational study included Wistar rats assigned to four groups: 1) ethanol consumption (EtOH+/CRS−), 2) stress exposure (EtOH−/CRS+), 3) both ethanol and stress exposure (EtOH+/CRS+), and 4) control group (EtOH−/CRS−). Our results showed that chronic stress did not affect ethanol intake but led to reduced body weight gain, elevated corticosterone levels, and impaired recognition memory. Structural MRI revealed that both exposures produced additive brain volume changes in olfactory bulb, orbitofrontal cortex, caudate-putamen, hippocampus, and cerebellum. Functional connectivity analysis using network-based statistics identified disrupted cortical-subcortical connections. Results found here were sex-dependent in terms of volumetric changes (higher effects on males) and functional connectivity (higher effects on females). Findings suggest sex-dependent mechanisms where both chronic- ethanol intake and stress affect brain plasticity during neurodevelopment. Understanding region-specific vulnerabilities is crucial for addressing alcohol use disorders and stress-related neuropathology.

Rasgado-Toledo, et al. reported sex-dependent and region-specific effects of combined ethanol exposure and chronic stress on both the rat brain volume and functional networks, affecting its plasticity during neurodevelopment.

Graphical Abstract