Elsevier

Alcohol

Volume 48, Issue 3, May 2014, Pages 235-241
Alcohol

“Drinking in the dark” (DID) procedures: A model of binge-like ethanol drinking in non-dependent mice

https://doi.org/10.1016/j.alcohol.2013.08.005Get rights and content

Abstract

This review provides an overview of an animal model of binge-like ethanol drinking that has come to be called “drinking in the dark” (DID), a procedure that promotes high levels of ethanol drinking and pharmacologically relevant blood ethanol concentrations (BECs) in ethanol-preferring strains of mice. Originally described by Rhodes, Best, Belknap, Finn, and Crabbe (2005), the most common variation of the DID procedure, using singly housed mice, involves replacing the water bottle with a bottle containing 20% ethanol for 2–4 h, beginning 3 h into the dark cycle. Using this procedure, high ethanol drinking strains of mice (e.g., C57BL/6J) typically consume enough ethanol to achieve BECs greater than 100 mg/dL and to exhibit behavioral evidence of intoxication. This limited access procedure takes advantage of the time in the animal's dark cycle in which the levels of ingestive behaviors are high, yet high ethanol intake does not appear to stem from caloric need. Mice have the choice of drinking or avoiding the ethanol solution, eliminating the stressful conditions that are inherent in other models of binge-like ethanol exposure in which ethanol is administered by the experimenter, and in some cases, potentially painful. The DID procedure is a high throughput approach that does not require extensive training or the inclusion of sweet compounds to motivate high levels of ethanol intake. The high throughput nature of the DID procedure makes it useful for rapid screening of pharmacological targets that are protective against binge-like drinking and for identifying strains of mice that exhibit binge-like drinking behavior. Additionally, the simplicity of DID procedures allows for easy integration into other paradigms, such as prenatal ethanol exposure and adolescent ethanol drinking. It is suggested that the DID model is a useful tool for studying the neurobiology and genetics underlying binge-like ethanol drinking, and may be useful for studying the transition to ethanol dependence.

Section snippets

DID procedures and influencing factors

Rhodes and colleagues tested a variety of factors that influence the amount of ethanol consumed by mice using variations of the DID procedure. Variations included ethanol concentration, the length of time into the dark cycle that ethanol was offered, the source from which the experimental mice were obtained, and mouse sex and strain (Rhodes et al., 2005). The general DID procedure implemented by Rhodes et al. (2005) was to house C57BL/6J mice (or other strains under consideration) individually

The advantages of DID procedures in modeling binge-like ethanol drinking

One of the clear advantages of DID is that it promotes pharmacologically meaningful BECs in an experimenter-defined limited access time frame (Crabbe et al., 2011). Because ethanol access is limited to a relatively short period of time, one can more easily assess the effects of pharmacological compounds on binge-like ethanol intake, especially in cases where the actions of a drug are short-term (i.e., 4 h or less). Further, as noted above, mice exhibit behavioral intoxication with DID and

Considerations for the DID model

While there are clear advantages to the DID procedure relative to other models of binge-like ethanol consumption/exposure, there are potential limitations with the model which should be considered. As noted above, the DID procedure takes advantage of a time in the animal's circadian rhythm associated with high levels of ingestive behavior. Clearly, administration of ethanol within the animal's dark cycle is a key component to the high level of ethanol intake associated with DID procedures. In

Future directions with DID procedures

Additional research is needed to a) further characterize and potentially improve DID procedures, b) understand the neurobiology and mechanisms that modulate binge-like ethanol drinking with DID procedures, and c) discover ways to expand the utility of the DID procedure. As noted above, much has been done to characterize the factors that influence the level of binge-like ethanol drinking with DID procedures. Thus, providing 20% ethanol in place of water for 2–4 h beginning 3 h into the dark

Acknowledgments

This work was supported by National Institute of Health grants AA022048, AA013573, and AA015148.

References (63)

  • C.A. Okoro et al.

    Binge drinking and health-related quality of life: do popular perceptions match reality?

    American Journal of Preventive Medicine

    (2004)
  • J.S. Rhodes et al.

    Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice

    Physiology & Behavior

    (2005)
  • M. Roberto et al.

    Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence

    Biological Psychiatry

    (2010)
  • J.P. Shepherd et al.

    Relations between alcohol, violence and victimization in adolescence

    Journal of Adolescence

    (2006)
  • R. Spanagel et al.

    Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat

    European Journal of Pharmacology

    (1996)
  • G.M. Sprow et al.

    The neurobiology of binge-like ethanol drinking: evidence from rodent models

    Physiology and Behavior

    (2012)
  • L. Vidal et al.

    Changes in neuropeptide Y immunoreactivity and transcript levels in circadian system structures of the diurnal rodent, the thirteen-lined ground squirrel

    Brain Research

    (2006)
  • L. Wang et al.

    Peripheral ghrelin selectively increases Fos expression in neuropeptide Y – synthesizing neurons in mouse hypothalamic arcuate nucleus

    Neuroscience Letters

    (2002)
  • S. Bake et al.

    Ethanol exposure during pregnancy persistently attenuates cranially directed blood flow in the developing fetus: evidence from ultrasound imaging in a murine second trimester equivalent model

    Alcoholism: Clinical and Experimental Research

    (2012)
  • A.M. Barkley-Levenson et al.

    Ethanol drinking microstructure of a high drinking in the dark selected mouse line

    Alcoholism: Clinical and Experimental Research

    (2012)
  • H.C. Becker et al.

    Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice

    Alcoholism: Clinical and Experimental Research

    (2004)
  • J.K. Belknap et al.

    Voluntary consumption of ethanol in 15 inbred mouse strains

    Psychopharmacology

    (1993)
  • Y.A. Blednov et al.

    Hybrid C57BL/6J x FVB/NJ mice drink more alcohol than do C57BL/6J mice

    Alcoholism: Clinical and Experimental Research

    (2005)
  • S.L. Boehm et al.

    Using drinking in the dark to model prenatal binge-like exposure to ethanol in C57BL/6J mice

    Developmental Psychobiology

    (2008)
  • B.R. Cox et al.

    Repeated cycles of binge-like ethanol (EtOH)-drinking in male C57BL/6J mice augments subsequent voluntary EtOH intake but not other dependence-like phenotypes

    Alcoholism: Clinical and Experimental Research

    (2013)
  • D.K. Cozzoli et al.

    Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional implications for alcoholism

    The Journal of Neuroscience

    (2009)
  • J.C. Crabbe et al.

    Preclinical studies of alcohol binge drinking

    Annals of the New York Academy of Sciences

    (2011)
  • V.P. Dole et al.

    Toward an analogue of alcoholism in mice: scale factors in the model

    Proceedings of the National Academy of Sciences of the United States of America

    (1984)
  • A.Z. Fan et al.

    Association of lifetime alcohol drinking trajectories with cardiometabolic risk

    The Journal of Clinical Endocrinology and Metabolism

    (2008)
  • W.J. Giardino et al.

    CRF1 receptor signaling regulates food and fluid intake in the drinking-in-the-dark model of binge alcohol consumption

    Alcoholism: Clinical and Experimental Research

    (2013)
  • A.E. Goudriaan et al.

    Decision making and binge drinking: a longitudinal study

    Alcoholism: Clinical and Experimental Research

    (2007)
  • Cited by (0)

    View full text