Alcohol and fear conditioning produce strain-specific changes in the dorsal hippocampal transcriptome of adolescent C57BL/6J and DBA/2J mice

Adolescent sensitivity to alcohol is predictive of later alcohol use and is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to dorsal hippocampus-dependent contextual fear learning deficits after acute alcohol exposure. To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression via RNA-sequencing after alcohol and/or fear conditioning across male and female C57BL/6J and DBA/2J adolescents. Strains exhibited dramatic differences in dorsal hippocampal gene expression. Specifically, C57BL/6J and DBA/2J strains differed in 3526 transcripts in males and 2675 transcripts in females. We identified pathways likely to be involved in mediating alcohol’s effects on learning, including networks associated with Chrna7 and Fmr1. These findings provide insight into the mechanisms underlying strain differences in alcohol’s effects on learning and suggest that different biological networks are recruited for learning based on genetics, sex, and alcohol exposure. We conducted RNA-sequencing to compare dorsal hippocampus gene expression from male and female adolescent mice (C57BL/6J and DBA/2J strains) after an acute EtOH (1.5 g/kg) or saline injection and fear conditioning (FC) or no fear conditioning control (noFC) conditions.