# Chronic intermittent ethanol vapor exposure alters local c‐Fos and functional connectivity patterns evoked by alcohol cues

## TL;DR

Chronic ethanol exposure in rats changes brain activity and connections when they are exposed to alcohol-related cues.

## Contribution

This study reveals region-specific changes in c-Fos and functional connectivity due to chronic ethanol exposure.

## Key findings

- CIE vapor exposure increased cue-evoked c-Fos levels in the prelimbic mPFC.
- CIE exposure altered functional connectivity patterns across brain regions.
- Perfusion timing also influenced functional connectivity in CIE-exposed rats.

## Abstract

Chronic intermittent ethanol (CIE) vapor inhalation is a widely used model for studying alcohol dependence. Additionally, cues paired with ethanol can drive and invigorate seeking behavior. However, the impact of ethanol‐paired cues on neural activation following a history of CIE vapor exposure remains poorly understood. Here, we examined the impact of ethanol‐paired cues in rats with or without a history of CIE vapor exposure on neuronal activation in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and the hippocampus (HPC) using c‐Fos as a marker.

Male and female Long–Evans rats with a history of air or CIE vapor exposure were exposed to previously learned alcohol‐associated cues under extinction conditions. Rats were perfused either immediately following cue exposure or with a delay to allow the development of c‐Fos protein. c‐Fos expression levels were analyzed in the mPFC, NAc, and HPC.

CIE vapor exposure led to a region‐specific effect on cue‐evoked c‐Fos levels, with enhanced cue‐evoked c‐Fos levels observed in the prelimbic mPFC of CIE rats. Correlation analysis of c‐Fos expression across brain regions revealed that CIE vapor exposure also led to altered functional connectivity patterns.

Our results suggest that CIE vapor exposure affects cue‐evoked c‐Fos expression in the prelimbic mPFC as well as influencing functional connectivity across regions.

How chronic intermittent ethanol (CIE) vapor exposure impacts alcohol cue‐evoked responses is not clear. We analyzed c‐Fos expression in the mPFC, NAc, and the hippocampus in CIE‐exposed rats perfused at different time points. CIE vapor‐exposed rats showed altered c‐Fos levels only in the PL mPFC, and both CIE and perfusion timing had an impact on functional connectivity across regions. Our results suggest that previous ethanol exposure can affect subsequent ethanol cue‐evoked neural activation and functional connectivity patterns.