Mice Exposed to Chronic low‐dose Ethanol Exhibit Reduced Sensitivity to Changes in Magnitude of Reward

Abstract

While approximately 2 billion individuals consume alcohol worldwide, the majority of these individuals to not exhibit drinking patterns consistent with alcohol use disorders (AUDs). Efforts have been made in investigating and characterizing the adverse effects on learning, memory and reward seeking with individuals afflicted with AUDs in a pursuit of therapeutic advancements. However, sub‐diagnostic alcohol effects have been understudied, despite the large number of low‐dose alcohol drinkers and the potential for low dose alcohol to impact both brain and behavior.Data from our lab has shown that low‐dose alcohol exposure enhances reward motivation in male, but not female, mice, but the mechanism of this is effect is unclear. Thus, we investigated the effects of low‐dose alcohol exposure on sensitivity to change in reward magnitude. A group of adult male C57BL6J mice were trained to self‐administer a 20 ul sucrose reward and received either a low‐dose ethanol (0.5g/kg) or saline injection 1 hour after training. To assess motivation, we used a progressive ratio (PR) task in which the effort required to earn the sucrose reward was increased linearly. Mice received multiple counterbalanced PR sessions in which the progressive schedule remained the same, but the reward magnitude was changed from 20ul (baseline) to 35ul, 25ul, 15ul or 5ul in counterbalanced sessions.Consistent with sensitivity to changes in reward value, saline control mice reduced or increased responding when reward volume was reduced or increased, respectively. Similar to saline controls, chronic low‐dose ethanol exposed mice increased their responding when reward volumes were increased compared to the 20ul baseline. However, ethanol exposed mice did not reduce responding to small reductions in reward magnitude. This observation in low‐dose ethanol mice suggests either a failure to detect reductions in reward magnitude or a dissociation between reduced reward magnitude and behavioral response. This lack of strategizing behavior to maintain effort‐to‐reward balance by ethanol exposed mice may imply that chronic low‐dose ethanol exposed mice may perceive greater reward value than controls even at reduced volume and implicates even low‐dose ethanol as a contributor to aberrant reward processing.