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

被引:37
作者
Crabbe, J. C. [1 ,2 ,3 ]
Metten, P. [1 ,2 ,3 ]
Belknap, J. K. [1 ,2 ,3 ]
Spence, S. E. [1 ,2 ,3 ]
Cameron, A. J. [1 ,2 ,3 ]
Schlumbohm, J. P. [1 ,2 ,3 ]
Huang, L. C. [1 ,2 ,3 ]
Barkley-Levenson, A. M. [1 ,2 ,3 ]
Ford, M. M. [3 ,4 ]
Phillips, T. J. [1 ,2 ,3 ]
机构
[1] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA
[2] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA
[3] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA
[4] Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Portland, OR 97201 USA
关键词
Binge; ethanol consumption; ethanol withdrawal; genetics; selective breeding; MOUSE STRAIN DIFFERENCES; ALCOHOL-CONSUMPTION; INBRED STRAINS; DRINKING; WITHDRAWAL; INTOXICATION; ACQUISITION; PREFERENCE; INTENSITY; SEVERITY;
D O I
10.1111/gbb.12105
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
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.
引用
收藏
页码:236 / 246
页数:11
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