Progress in a Replicated Selection for Elevated Blood Ethanol Concentrations in HDID Mice


J. C. Crabbe, P. Metten, J. K. Belknap, S. E. Spence, A. J. Cameron, J. P. Schlumbohm, L. C. Huang, A. M. Barkley-Levenson, M. Ford, and T. J. Phillip


Drinking in the Dark (DID) is a limited access ethanol drinking phenotype in mice. High Drinking in the Dark (HDID-1) mice have been bred for 27 selected generations (S27) for elevated blood ethanol concentrations (BECs) after a 4 hr period of access to 20% ethanol. A second replicate line (HDID-2) was started later from the same founder population and is currently in S20. An initial report of response to selection in HDID-1 was published after S11. This paper reports genetic and behavioral characteristics of both lines in comparison with the HS controls. Heritability is low in both replicates (h2 = 0.09) but the lines have shown 4-5 fold increases in BEC since S0; 80% of HDID-1 and 60% of HDID-2 mice reach BECs greater than 1.0 mg/ml. Several hours after a DID test, HDID mice show mild signs of withdrawal. Although not considered during selection, intake of ethanol (g/kg) during the DID test increased by approximately 80% in HDID-1 and 60% in HDID-2. Common genetic influences were more important than environmental influences in determining the similarity between BEC and intake for HDID mice. Analysis of the partitioning of intake showed that 60% of intake is concentrated in the last 2 hr of the 4 hr session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4 hr of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol.


Genes Brain Behav. 2014 Feb; 13(2): 236–246. 2013 Dec 6. doi: 10.1111/gbb.12105