Additive influences of acute early life stress and sex on vulnerability for aversion-resistant alcohol drinking

Addict Biol. 2020 Nov;25(6):e12829. doi: 10.1111/adb.12829. Epub 2019 Oct 27.


Acute early life stress (ELS) alters stress system functioning in adulthood and increases susceptibility to posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). The current study assessed the effects of acute, infant ELS on alcohol drinking, including aversion-resistant drinking, in male and female Long Evans rats. Acute ELS was induced using a stress-enhanced fear learning (SEFL) protocol that consisted of 15 footshocks delivered on postnatal day (PND) 17. Alcohol drinking during adolescence and adulthood was measured with a two-bottle choice intermittent alcohol access paradigm. Aversion-resistant drinking was assessed in adulthood by adding quinine (0.01, 0.1, and 1.0 g/L) to the alcohol bottle after 5 to 6 weeks and 11 to 12 weeks of drinking. ELS had minimal influences on adolescent and adult alcohol consumption and preference. However, ELS, sex, and alcohol exposure history all influenced aversion-resistant alcohol drinking in an additive fashion. Higher concentrations of quinine were tolerated in females, ELS-exposed rats, and after 11 to 12 weeks of drinking. Tests of quinine sensitivity in a separate cohort of animals found that rats can detect concentrations of quinine as low as 0.001 g/L in water and that quinine sensitivity is not influenced by sex or ELS exposure. These results agree with reports of sex differences in aversion-resistant drinking and are the first to demonstrate an influence of ELS on this behavior. Our results also suggest that a single traumatic stress exposure in infancy may be a promising model of comorbid PTSD and AUD and useful in studying the interactions between ELS, sex, and alcohol dependence.

Keywords: (6) alcohol; compulsive drinking; early life stress; quinine; sex differences; stress enhanced fear learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking* / psychology
  • Alcoholism / psychology
  • Animals
  • Drug-Seeking Behavior*
  • Fear / psychology
  • Female
  • Male
  • Quinine
  • Rats
  • Rats, Long-Evans
  • Sex Characteristics*
  • Stress, Psychological*


  • Quinine