Delay Discounting Predicts Behavioral Sensitization to Ethanol in Outbred WSC Mice

Abstract

Background: Alcoholic individuals discount the value of future rewards more steeply than social drinkers, which is viewed as symptomatic of higher levels of impulsivity. However, the mechanisms underlying this difference are unknown. This study examined 2 hypotheses about the relationship between discounting and ethanol's effects in mice: (1) steep discounters are less sensitive to the initial stimulant-like effects of ethanol and (2) steep discounters exhibit greater behavioral adaptation to stimulant effects with repeated ethanol exposure. Methods: An adjusting amount procedure was used to assess discounting as a function of delay in ethanol-naïve genetically heterogeneous WSC mice. Mice chose between a small amount of sucrose solution delivered immediately and 19.5 μL delivered following a delay (0, 2, 4, 8, or 12 seconds, varied between sessions). Within sessions, the amount (μL) of immediate sucrose was adjusted until animals became indifferent between the immediate and specific delayed reward. Hyperbolic discount functions were fitted to quantify the degree of delay discounting. Then, in a within-subjects design over 13 days, mice received a pattern of daily injections of saline or ethanol, and after certain treatments their locomotor activity was assessed for 15 minutes. Results: Animals with steeper discount functions (greater impulsivity) tended to exhibit less locomotor stimulation on their initial exposure to ethanol. However, steeper discounting was positively associated with increases in locomotor activity after repeated exposure (sensitization), indicating that steep discounters showed higher levels of sensitization to the stimulating effects of ethanol. Conclusions: These results suggest 2 behavioral effects of ethanol, associated with an increased risk for alcohol abuse, that are associated with variations in delay discounting.