Gehle V M, Erwin V G
Alcohol Research Center and School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Alcohol Clin Exp Res. 1998 Apr;22(2):401-8.
The C57BL/6, DBA/2, and recombinant inbred (RI) strains derived from them (BxD RIs) are the most frequently studied mouse strains with regard to genetic regulation of voluntary ethanol consumption (YEC). We have studied VEC in an alternate genetic model provided by the LSxSS RIs. These RI strains exhibit phenotypic extremes in VEC comparable to the C57BL/6 and DBA/2 mice and genotype-dependent sex differences in drinking behavior. A correlational analysis between various ethanol-related behaviors suggests genetic independence of VEC from high-dose neurosensitivity (sleep time), acute ethanol tolerance, hypothermia, and low-dose locomotor activity. A search for quantitative trait loci identified a number of putative quantitative trait loci (QTL), three of which are identical to those previously reported for 10% ethanol drinking in the BxD RIs. We also find a significant correlation between low-affinity neurotensin receptor densities (NTRL) in the frontal cortex and VEC, and more common QTL between these two phenotypes than expected by chance. This suggests a role for frontal cortex NTRL in regulating voluntary ethanol intake.
C57BL/6、DBA/2以及由它们衍生而来的重组近交(RI)品系(BxD RI)是在自愿乙醇消耗(YEC)的遗传调控方面研究最为频繁的小鼠品系。我们在由LSxSS RI提供的另一种遗传模型中研究了自愿乙醇消耗(VEC)。这些RI品系在VEC方面表现出与C57BL/6和DBA/2小鼠相当的表型极端情况,并且在饮酒行为上存在基因型依赖性的性别差异。对各种与乙醇相关行为之间的相关性分析表明,VEC与高剂量神经敏感性(睡眠时间)、急性乙醇耐受性、体温过低以及低剂量运动活性在遗传上相互独立。对数量性状基因座的搜索鉴定出了一些假定的数量性状基因座(QTL),其中三个与先前在BxD RI中报道的10%乙醇饮用相关的基因座相同。我们还发现额叶皮质中的低亲和力神经降压素受体密度(NTRL)与VEC之间存在显著相关性,并且这两种表型之间的常见QTL比偶然预期的更多。这表明额叶皮质NTRL在调节自愿乙醇摄入中发挥作用。