Sex and individual differences in the effect of chronic low-dose ethanol on behavioral strategy selection

Abstract

Background: The development of an alcohol use disorder (AUD) involves impaired behavioral control and flexibility. Behavioral inflexibility includes an inability to shift behavior in response to changes in behavioral outcomes. Low levels of ethanol drinking may promote the formation of inflexible, habitual reward seeking, but this may depend on the timing of ethanol exposure in relation to learning. The goal of this study was to determine whether a history of low-dose ethanol exposure promoted contingency-insensitive sucrose seeking and altered behavioral strategy selection.

Methods: Male and female C57BL/6J mice were trained to perform a response (lever press) for sucrose on two different reinforcement schedules: one that is thought to promote inflexible responding (random interval) and one that maintains flexible responding (variable ratio [VR]). Following instrumental training each day, mice were exposed to saline or low-dose ethanol (0.5 g/kg; i.p.) either proximal (1 h after) or distal (4 h after) to learning. Mice were then tested for sensitivity to changes in contingency in a contingency degradation test.

Results: A history of low-dose ethanol exposure shifted behavioral strategy selection, as measured by reward tracking behavior, but this depended on sex and reinforcement schedule history. Both male and female mice used different strategies depending on the reinforcement schedule, but only males exhibited ethanol-induced shifts in strategy selection. A history of low-dose ethanol exposure did not impact contingency sensitivity in males but promoted insensitivity in females specifically on the VR lever.

Conclusions: Female mice show distinct behavioral effects of repeated, low-dose ethanol exposure as compared to males, with sex differences in the use of reward tracking strategies to guide behavior. Future studies should investigate sex differences in the neural consequences of chronic low-dose ethanol exposure that may underlie behavioral changes.