The effect of repeated exposure to ethanol on pre-existing fear memories in rats

RATIONALE: There is a high degree of comorbidity between alcohol use disorder and post-traumatic stress disorder (PTSD), but little is known about the interactions of ethanol with traumatic memories. OBJECTIVES: Using auditory fear conditioning in rats, we asked if repeated exposure to ethanol could modify the retrieval of fear memories acquired prior to ethanol exposure. METHODS: Following auditory fear conditioning, Sprague-Dawley rats were given daily injections of ethanol (1.5 g/kg) or saline over 5 days. Two days later, they were given 20 trials of extinction training and then tested for extinction memory the following day. In a separate experiment, conditioned rats were given repeated ethanol injections and processed for c-Fos immunohistochemistry following a fear retrieval session. RESULTS: Two days following the cessation of ethanol, the magnitude of conditioned fear responses (freezing and suppression of bar pressing) was significantly increased. This increase persisted the following day. Waiting 10 days following cessation of ethanol eliminated the effect on fear retrieval. In rats conditioned with low shock levels, repeated exposure to ethanol converted a sub-threshold fear memory into a supra-threshold fear memory. It also increased c-Fos expression in the prelimbic prefrontal cortex, paraventricular thalamus, and the central and basolateral nuclei of the amygdala, areas implicated in the retrieval of fear memories. CONCLUSIONS: These results suggest that repeated exposure to ethanol may exacerbate pre-existing traumatic memories.