4.2 Article

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

Journal

GENES BRAIN AND BEHAVIOR
Volume 13, Issue 2, Pages 236-246

Publisher

WILEY
DOI: 10.1111/gbb.12105

Keywords

Binge; ethanol consumption; ethanol withdrawal; genetics; selective breeding

Funding

  1. US Department of Veterans Affairs
  2. NIH, NIAAA [AA013519, AA010760, AA020245]
  3. NIH [OD11092]
  4. Dept. of the Army/DoD-TATRC Grant [10245005.05.]
  5. NIAAA [AA022009]
  6. OHSU Graduate Research Scholar Award

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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-h 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 article reports genetic and behavioral characteristics of both lines in comparison with the HS controls. Heritability is low in both replicates (h(2)=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 1.0mg/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 2h of the 4h session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4h of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol.

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