Quantitative trait loci for sensitivity to acute ethanol and ethanol consummatory behaviors in rats.
Quantitative trait loci for sensitivity to acute ethanol and ethanol consummatory behaviors in rats.
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DOI：
10.1016/j.alcohol.2017.08.002
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Radcliffe RA
中科院分区：
文献类型：
--
作者：
Mandt BH;Larson C;Fay T;Bludeau P;Allen RM;Deitrich RA;Radcliffe RA
对酒精的初始反应较低的个体（即，乙醇（EtOH）在以后的生活中有更大的风险发展为酒精滥用或依赖。与人类相似，在大鼠中也可以观察到EtOH敏感性的个体差异，几个实验室已经使用这些个体差异来产生急性EtOH敏感性不同的选择性繁殖大鼠。我们研究了两组这样的老鼠（近交高或低酒精敏感性品系，分别为IHAS或ILAS;近交酒精耐受性或非耐受性品系，分别为IAT和IANT），并且已经使用重组同类系证实了先前针对这些急性差异绘制的数量性状基因座（QTL）;然而，这些大鼠急性敏感性与乙醇饮用之间的关系尚未确定。因此，在这里，我们测试的假设，QTL的变化在初始低敏感性EtOH也将调节变化的EtOH饮用行为。使用操作性自我给药或间歇性进入两瓶选择程序，对单独组的选择性近交亲本和同类大鼠进行了翻正反应丧失（LORR）检测，并评估了EtOH消耗行为。LORR测试证实了LORR持续时间QTL的存在下，在所有的同类;然而，缺乏相应的差异，在恢复的翻正反应的血液乙醇浓度表明，这些QTL可能介导的差异乙醇代谢，而不是在神经元的敏感性。IHAS/ILAS衍生的同类大鼠在操作性自我给药期间的任何时间点均与亲代大鼠无差异。IAT/IANT衍生的同类大鼠表现出小，但显着，增加乙醇消耗相对于亲株仅在初始阶段的操作性自我管理。与操作性测试相反，IHAS/ILAS衍生的同类大鼠在间歇性访问测试期间显示出比亲代大鼠显著更大的EtOH消耗和偏好。然而，在间歇性访问期间，IAT/IANT同类大鼠与亲代大鼠之间无差异。这些数据支持以下假设：至少对于IHAS/ILAS衍生的同类大鼠，初始EtOH敏感性和EtOH消耗量之间存在遗传关系。然而，我们目前的研究不能排除药代动力学或口味偏好因素对大鼠反应的影响，也不能排除连锁效应的可能性，因为QTL区间相当大;即，不同的基因可能介导急性敏感性和饮酒反应。
Individuals with a low initial response to alcohol (i.e., ethanol; EtOH) are at greater risk of developing alcohol abuse or dependence later in life. Similar to humans, individual differences in EtOH sensitivity also can be seen in rats, and several laboratories have used these individual differences to generate selectively bred rats that differ in acute EtOH sensitivity. We have worked with two sets of such rats (Inbred High or Low Alcohol Sensitivity strains, IHAS or ILAS, respectively; Inbred Alcohol Tolerant or Non-Tolerant strains, IAT and IANT, respectively) and have confirmed previously mapped quantitative trait loci (QTL) for these acute differences with the use of recombinant congenic lines; however, the relationship between acute sensitivity and EtOH drinking in these rats has yet to be determined. Thus, here we tested the hypothesis that QTLs underlying variation in initial low sensitivity to EtOH also will modulate variation in EtOH drinking behaviors. Separate groups of selectively inbred parent and congenic rats were tested for the loss of righting response (LORR) and also assessed for EtOH consummatory behavior using either operant self-administration or an intermittent access two-bottle choice procedure. LORR testing confirmed the presence of a LORR duration QTL in all of the congenics; however, the lack of a corresponding difference in blood EtOH concentration at the regain of the righting response suggests that these QTLs may be mediating a difference in EtOH metabolism rather than in neuronal sensitivity. IHAS/ILAS derived congenic rats did not differ from parent rats at any point during operant self-administration. IAT/IANT derived congenic rats showed small, but significant, increases in EtOH consumption relative to the parent strains only during the initial stages of operant self-administration. In contrast to operant testing, IHAS/ILAS derived congenic rats showed significantly greater EtOH consumption and preference than parent rats during intermittent access testing. There were not differences, however, between IAT/IANT congenic and parent rats during intermittent access. These data support the hypothesis that there is a genetic relationship between initial EtOH sensitivity and EtOH consumption, at least for the IHAS/ILAS derived congenic rats. Our current studies, however, cannot eliminate pharmacokinetic or taste preference factors as contributing to the rats’ responses nor can we eliminate the possibility of a linkage effect because of the fairly large size of the QTL intervals; i.e., distinct genes may be mediating the acute sensitivity and drinking responses.
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DOI：
10.1111/j.1530-0277.1992.tb00634.x
发表时间：
1992-02-01
影响因子：
3.2
作者：
DRASKI, LJ;SPUHLER, KP;DEITRICH, RA
通讯作者：
DEITRICH, RA
DOI：
10.1111/j.1601-183x.2009.00496.x
发表时间：
2009-08
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Radcliffe RA;Erwin VG;Bludeau P;Deng X;Fay T;Floyd KL;Deitrich RA
通讯作者：
Deitrich RA
DOI：
10.1111/acer.12678
发表时间：
2015-04
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bennett B;Larson C;Richmond PA;Odell AT;Saba LM;Tabakoff B;Dowell R;Radcliffe RA
通讯作者：
Radcliffe RA
影响因子：
2.6
作者：
Radcliffe, RA;Hoffmann, SE;Deitrich, RA
通讯作者：
Deitrich, RA
影响因子：
2.3
作者：
SARVIHARJU, M;KORPI, ER
通讯作者：
KORPI, ER