Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.
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 1.0 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 h of the 4 h session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4 h of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol.
Portland Alcohol Research Center; Veterans Affairs Medical Center; Department of Behavioral Neuroscience.
J C
JC
Crabbe
P
P
Metten
J K
JK
Belknap
S E
SE
Spence
A J
AJ
Cameron
J P
JP
Schlumbohm
L C
LC
Huang
A M
AM
Barkley-Levenson
M M
MM
Ford
T J
TJ
Phillips
D000818:Animals; D063425:Binge Drinking / Q000235:genetics*; D000431:Ethanol / Q000097:blood*; D005260:Female; D007178:Inbreeding; D008297:Male; D051379:Mice; D012641:Selection, Genetic
D000431:Ethanol
Binge; ethanol consumption; ethanol withdrawal; genetics; selective breeding