A history of low dose ethanol modulates ventral hippocampus activity during motivated behavior

Abstract

More than half of the 130 million people in the U.S. who consumed alcohol within the last month did so at a level that did not meet diagnostic criteria for an alcohol binge. However, even these sub diagnostic drinking levels can have neurobehavioral outcomes. Clinical studies have shown that low levels of acute ethanol drinking soon after learning can enhance task consolidation and memory recall. Our preclinical data in C57BL6J mice show that a history of repeated, low dose ethanol (0.5g/kg) exposure increases sucrose reward motivation as measured by progressive ratio. The ventral hippocampus (vHPC) is increasingly considered a critical contributor to reward seeking and has been shown to be sensitive to chronic ethanol exposure at higher doses. The present study sought to determine whether daily, post‐training, low dose ethanol exposure can modulate vHPC activity during motivated behavior. To investigate this, we implanted mice with an electrode array to record vHPC neural activity during performance of a progressive ratio task. We also investigated vHPC activity around important behavioral events in the task, including lever pressing (when the animal is seeking the reward) and magazine entries (when the animal is checking for reward delivery). Our results demonstrate that saline control mice show suppression of vHPC activity following a lever press, while mice with a history of low dose ethanol exposure exhibit this suppression prior to a lever press. In contrast, both saline and ethanol‐exposed mice exhibit similar vHPC activity patterns surrounding magazine entry. These results suggest that a history of post‐training low dose ethanol exposure modulates vHPC activity during reward seeking. Further, this shift in vHPC suppression around a lever press may be associated with the enhanced motivation for sucrose observed in ethanol‐exposed mice. Future studies will use optogenetics to determine whether this shift in activity contributes to heightened reward motivation in ethanol exposed mice. A greater understanding of the neurobiological substrates impacted by ethanol exposure can help identify factors placing casual drinkers at risk for transition to alcohol use disorder.