Interaction of stress and alcohol on discriminating fear from safety and reward in male and female rats

Psychopharmacology (Berl). 2023 Mar;240(3):609-621. doi: 10.1007/s00213-022-06206-5. Epub 2022 Aug 12.


Rationale: Stressful events can have lasting and impactful effects on behavior, especially in terms of appropriate fear regulation and reward seeking. Our prior work in rats has shown baseline sex differences in fear expression and sucrose seeking in a discriminative reward-fear-safety conditioning task.

Objectives: The objectives of the current study were to determine how prior stress may affect alcohol consumption across a reward-fear-safety learning task, and how prior alcohol history may interact with stress to impact learning in this task.

Methods: Male and female Long Evans rats were given home cage intermittent 24 h access to both water and alcohol for 5 weeks. A subset of rats then received exposure to stress (15 unsignaled footshocks), while remaining unstressed rats received context exposure without shock. One week later, all rats were trained on the same reward-fear-safety cue task while having continuous home cage access to both water and alcohol.

Results: All rats increased consumption (g/kg/24 h) across the 5 weeks of intermittent access, with females showing higher consumption levels. Stress exposure did not alter alcohol consumption in the week following stress, but did increase home cage alcohol consumption during later reward-fear-safety cue learning. Stress in both sexes also elevated freezing levels to the reward cue resulting in decreased sucrose seeking and was positively correlated with home cage alcohol consumption.

Conclusions: While stress increased drinking in both males and females, the effects of stress were particularly pronounced in females, indicating our results could be capturing a higher propensity for females to display stress-induced drinking.

Keywords: Alcohol; Fear; Reward; Safety; Sex differences; Stress.

MeSH terms

  • Alcohol Drinking
  • Animals
  • Ethanol* / pharmacology
  • Fear* / physiology
  • Female
  • Male
  • Rats
  • Rats, Long-Evans
  • Reward
  • Sucrose / pharmacology


  • Ethanol
  • Sucrose