Intermittent Ethanol-induced Fear Memory Impairment with Differential Hippocampal Activation in Male Mice

The limbic system, particularly the hippocampus and amygdala, are oft-studied and well-established regions for fear learning and memory and have been seen to critically underlie the encoding of contextual fear memory. Literature has shown that chronic ethanol consumption has a negative effect on hippocampal beta-dynorphin – a neuropeptide implicated in limbic LTP and fear-forming memories. The impact of self- administered chronic ethanol on hippocampal fear memory has not yet been investigated in mice. In this study, we exposed 3 cohorts of C57BL/6J mice to an intermittent-access ethanol protocol for 6 weeks followed by fear conditioning tests. We found significant differences in freezing behaviour between binge-like drinking mice and water controls on a trace conditioning protocol. Immunohistochemistry for c- Fos was performed, and significant differences were seen in CA1, CA3, and the dentate gyrus between binge-like mice and controls after fear exposure. These findings suggest that chronic ethanol consumption has a dampening effect on fear learning in mice and implicates differential hippocampal activation potentially underlying the behaviour seen.