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Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

J C Crabbe1, P Metten, J K Belknap

  • 1Portland Alcohol Research Center; Veterans Affairs Medical Center; Department of Behavioral Neuroscience.

Genes, Brain, and Behavior
|November 14, 2013
PubMed
Summary

High Drinking in the Dark (HDID) mice exhibit significantly elevated blood ethanol concentrations (BECs) and increased ethanol intake, despite low heritability. These mice show mild withdrawal signs and concentrated drinking patterns, with genetic factors influencing BEC and intake similarity.

Keywords:
Bingeethanol consumptionethanol withdrawalgeneticsselective breeding

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Area of Science:

  • Genetics
  • Neuroscience
  • Animal Behavior

Background:

  • The Drinking in the Dark (DID) model is a limited-access ethanol consumption paradigm in mice.
  • High Drinking in the Dark (HDID) mice have been selectively bred for increased blood ethanol concentrations (BECs).
  • Two replicate lines, HDID-1 (S27) and HDID-2 (S20), were developed from the same founder population.

Purpose of the Study:

  • To characterize the genetic and behavioral traits of HDID-1 and HDID-2 mouse lines.
  • To compare the selected lines with control HS mice.
  • To analyze the response to selection for elevated BECs.

Main Methods:

  • Selective breeding for 27 generations (HDID-1) and 20 generations (HDID-2) using the DID paradigm.
  • Measurement of blood ethanol concentrations (BECs) and ethanol intake (g/kg) during DID tests.
  • Assessment of withdrawal signs and ethanol elimination rates.

Main Results:

  • Both HDID lines show a 4-5 fold increase in BECs compared to controls, with low heritability (h²=0.09).
  • 80% of HDID-1 and 60% of HDID-2 mice achieve BECs >1.0 mg/ml.
  • Ethanol intake increased by 60-80% in HDID lines; genetic influences were more significant than environmental ones for BEC and intake correlation.
  • Drinking patterns showed concentration in the last 2 hours of the 4-hour session, with BECs peaking at 3-4 hours.
  • HDID mice exhibit mild withdrawal signs hours after DID and do not differ in alcohol elimination rates.

Conclusions:

  • Selective breeding effectively increased BECs in HDID mice, demonstrating the utility of the DID model for studying ethanol consumption.
  • Genetic factors play a crucial role in the relationship between ethanol intake and BECs in these selected lines.
  • HDID mice provide a valuable model for investigating the neurobiological underpinnings of high ethanol consumption and potential withdrawal symptoms.