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Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice
Published on: January 7, 2019
Ethanol sensitivity in high drinking in the dark selectively bred mice
John C Crabbe1, Lauren C Kruse, Alexandre M Colville
1Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, and VA Medical Center, Portland, OR 97239, USA. crabbe@ohsu.edu
Alcoholism, Clinical and Experimental Research
|February 10, 2012
Summary
Selective breeding created mice with high blood ethanol concentrations (BECs). These mice exhibit altered responses to ethanol (EtOH), indicating shared genetic influences on drinking behavior and EtOH sensitivity.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Selective breeding is used to develop mouse lines with high blood ethanol concentrations (BECs) after ethanol (EtOH) consumption during the dark phase.
- The High Drinking in the Dark-1 (HDID-1) and HDID-2 mouse lines were developed through this selective breeding process.
Purpose of the Study:
- To investigate genetic correlations between high Drinking in the Dark (DID) behavior and other ethanol-related traits.
- To compare the physiological and behavioral responses to ethanol in selectively bred high-drinking mice versus their progenitor stock.
Main Methods:
- Comparison of naïve HDID-1 and HDID-2 mice with the unselected HS/Npt progenitor stock.
- Assessment of various behavioral and physiological responses to acute ethanol exposure, including activity levels, motor coordination (foot slips, balance beam, rotarod), hypothermia, and loss of righting reflex.
- Analysis of ethanol metabolism to rule out its influence on observed responses.
Main Results:
- HDID-1 mice displayed reduced basal activity but increased ethanol-stimulated activity and heightened sensitivity to ethanol-induced foot slips compared to HS mice.
- HDID-1 mice showed decreased sensitivity to acute ethanol hypothermia but a prolonged duration of ethanol-induced loss of righting reflex.
- No significant differences were observed between HDID-1 and HS mice in balance beam or accelerating rotarod tests; results were not attributable to altered ethanol metabolism.
Conclusions:
- The findings suggest that genetic factors influencing the tendency to achieve high blood ethanol concentrations through drinking in the dark are shared with genetic factors controlling other ethanol responses.
- This supports the concept of common genetic underpinnings for various ethanol-related behaviors and physiological effects.
