Repeated light-dark phase shifts modulate voluntary ethanol intake in male and female high alcohol-drinking (HAD1) rats

Alcohol Clin Exp Res. 2007 Oct;31(10):1699-706. doi: 10.1111/j.1530-0277.2007.00476.x. Epub 2007 Aug 6.


Background: Chronic disruption of sleep and other circadian biological rhythms, such as occurs in shift work or in frequent transmeridian travel, appears to represent a significant source of allostatic load, leading to the emergence of stress-related physical and psychological illness. Recent animal experiments have shown that these negative health effects may be effectively modeled by exposure to repeated phase shifts of the daily light-dark (LD) cycle. As chronobiological disturbances are thought to promote relapse in abstinent alcoholics, and may also be associated with increased risk of subsequent alcohol abuse in nonalcoholic populations, the present experiment was designed to examine the effects of repeated LD phase shifts on voluntary ethanol intake in rats. A selectively bred, high alcohol-drinking (HAD1) rat line was utilized to increase the likelihood of excessive alcoholic-like drinking.

Methods: Male and female rats of the selectively bred HAD1 rat line were maintained individually under a LD 12:12 cycle with both ethanol (10% v/v) and water available continuously. Animals in the experimental group were subjected to repeated 6-hour LD phase advances at 3 to 4 week intervals, while control rats were maintained under a stable LD cycle throughout the study. Contact-sensing drinkometers were used to monitor circadian lick patterns, and ethanol and water intakes were recorded weekly.

Results: Control males showed progressively increasing ethanol intake and ethanol preference over the course of the study, but males exposed to chronic LD phase shifts exhibited gradual decreases in ethanol drinking. In contrast, control females displayed decreasing ethanol intake and ethanol preference over the course of the experiment, while females exposed to experimental LD phase shifts exhibited a slight increase in ethanol drinking.

Conclusions: Chronic circadian desynchrony induced by repeated LD phase shifts resulted in sex-specific modulation of voluntary ethanol intake, reducing ethanol intake in males while slightly increasing intake in females. While partially contrary to initial predictions, these results are consistent with extensive prior research showing that chronic stress may either increase or decrease ethanol intake, depending on strain, sex, stressor type, and experimental history. Thus, repeated LD phase shifts may provide a novel chronobiological model for the analysis of stress effects on alcohol intake.

Publication types

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

MeSH terms

  • Alcohol Drinking / physiopathology*
  • Alcoholism / physiopathology*
  • Animals
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / blood
  • Circadian Rhythm / physiology*
  • Disease Models, Animal
  • Drinking / physiology
  • Drinking Behavior / physiology*
  • Ethanol / administration & dosage
  • Ethanol / blood
  • Female
  • Male
  • Rats
  • Rats, Inbred Strains
  • Sex Characteristics


  • Central Nervous System Depressants
  • Ethanol