Effect of chronic alcohol exposure and single-prolonged stress on conditioned fear behavior

Behav Brain Res. 2025 Feb 4:477:115294. doi: 10.1016/j.bbr.2024.115294. Epub 2024 Oct 16.

Abstract

The present study investigated the impact of chronic intermittent ethanol (CIE) exposure and single-prolonged stress (SPS) on the acquisition of fear memories in both male and female Wistar rats. Adult rats were first subjected to CIE by vapor inhalation followed by SPS. Following a subsequent 8-day incubation period, the rats underwent a Pavlovian fear conditioning procedure (tone-shock pairings) followed by cued-tone extinction training, and then testing of extinction recall memory and fear renewal memory. In control animals that had not been exposed to either CIE or SPS, female rats exhibited significantly lower levels of freezing compared to male rats during tone-shock pairings. This lower level of freezing in female rats during conditioning was associated with an increased speed of movement compared to males. Also compared to males, female rats exhibited lower levels of fear extinction, recall, and renewal. Exposure to CIE, SPS, or CIE+SPS had no effect on freezing during the cued-conditioning, extinction, or extinction recall phases of the testing procedure in either sex. In fear renewal, CIE exposure decreased freezing in male but not female rats, while SPS increased freezing in female but not male rats. CIE exposure significantly reduced freezing during the fear renewal phase. Taken together, these results provide further evidence that male and female rats adopt different avoidance strategies for threat responding. These results also revealed that prior exposure to CIE, SPS, or CIE+SPS had minimal effects on threat responding using conditioned freezing as an indicator of fear responsivity.

Keywords: Chronic alcohol; Extinction; Fear conditioning; Freezing; Sex-differences; Single-prolonged stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / pharmacology
  • Conditioning, Classical* / drug effects
  • Conditioning, Classical* / physiology
  • Cues
  • Ethanol* / administration & dosage
  • Ethanol* / pharmacology
  • Extinction, Psychological* / drug effects
  • Extinction, Psychological* / physiology
  • Fear* / drug effects
  • Fear* / physiology
  • Female
  • Freezing Reaction, Cataleptic / drug effects
  • Freezing Reaction, Cataleptic / physiology
  • Male
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Rats
  • Rats, Wistar*
  • Sex Characteristics
  • Stress, Psychological* / physiopathology

Substances

  • Ethanol
  • Central Nervous System Depressants