How Does Alcohol Exposure Affect PTSD Symptoms and Brain Changes in Mice?

What you need to know

• Mice exposed to trauma and then alcohol showed impaired extinction of avoidance behavior and increased relapse of PTSD-like symptoms compared to mice not exposed to alcohol
• Alcohol exposure increased dendritic changes in the prelimbic cortex associated with trauma susceptibility
• Trauma-susceptible mice showed stronger preference for alcohol in a conditioned place preference test
• Alcohol did not affect trauma-induced changes in corticosterone or BDNF levels

Background

Post-traumatic stress disorder (PTSD) often co-occurs with alcohol use disorder, which can make PTSD symptoms more persistent and treatment resistant. However, the brain mechanisms underlying this relationship are not well understood. This study used a mouse model to examine how alcohol exposure affects PTSD-like symptoms and associated brain changes.

Methods

Male mice were exposed to a high-intensity footshock to induce PTSD-like symptoms. Eight days later, some mice underwent conditioned place preference training with ethanol injections. The researchers then conducted behavioral tests to assess fear sensitization, avoidance behavior, anxiety, extinction of avoidance, and relapse susceptibility. They also measured dendritic changes in the medial prefrontal cortex and levels of corticosterone and brain-derived neurotrophic factor (BDNF).

Key Findings

Behavioral effects of alcohol exposure

Trauma-susceptible mice exposed to alcohol showed:

• Delayed extinction of avoidance behavior toward the trauma-associated context
• Increased susceptibility to relapse of avoidance behavior
• Stronger preference for the alcohol-paired chamber in the conditioned place preference test

Alcohol exposure did not significantly affect fear sensitization or anxiety-like behavior.

Brain changes

• Alcohol exposure increased dendritic spine density and length in the prelimbic cortex of trauma-susceptible mice
• There was a positive correlation between relapse of avoidance behavior and dendritic changes in the prelimbic cortex
• Alcohol did not affect trauma-induced increases in corticosterone or decreases in BDNF

Implications

These findings suggest that alcohol use after trauma may make PTSD symptoms more persistent by altering brain plasticity, particularly in the prelimbic cortex. The study provides insight into potential neurobiological mechanisms underlying the relationship between PTSD and alcohol use disorder. Understanding these mechanisms could inform the development of more effective treatments for co-occurring PTSD and alcohol use problems.

Limitations

• The study only included male mice, so the findings may not generalize to females
• The alcohol administration method (injections) differs from voluntary consumption in humans
• The study did not include control groups receiving unpaired exposures to stimuli, limiting causal conclusions

Conclusions

• Alcohol exposure after trauma impaired extinction of avoidance behavior and increased relapse susceptibility in mice
• These behavioral effects were associated with increased dendritic changes in the prelimbic cortex
• The findings suggest alcohol may contribute to persistent PTSD symptoms by altering brain plasticity
• Further research is needed to determine if similar mechanisms occur in humans with co-occurring PTSD and alcohol use disorder