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

BACKGROUND 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.

METHODS 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.

RESULTS 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.

CONCLUSIONS 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.