Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice
Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice
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DOI：
10.1097/00000374-199809000-00008
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发表时间：
1998-09-01
影响因子：
3.2
通讯作者：
Cunningham, CL
中科院分区：
文献类型：
--
作者：
Risinger, FO;Cunningham, CL
对乙醇厌恶作用敏感性的遗传差异可能在酗酒行为和酗酒的发展中发挥重要作用。本研究检查了 20 只 BXD/Ty 重组近交系小鼠及其祖代近交系 C57BL/6J (B6) 和 DBA/2J (D2) 中乙醇诱导的条件性味觉厌恶的发展。成年雄性小鼠每 48 小时接受一次糖精味溶液 1 小时，持续 12 天。在除了第一个和最后一个糖精使用期之外的所有时间后，他们接受乙醇注射（0、2或4 g/kg，腹膜内注射）。不同组的未配对对照小鼠在获得水后1小时接受4g/kg的乙醇。盐水对照小鼠也用于检查对各种糖精浓度（0.019 至 4.864% w/v）的偏好。正如预期的那样，在味觉调节过程中糖精的消耗量以剂量依赖的方式在调节试验中下降，表明乙醇诱导的条件性味觉厌恶的发展。使用最近发表的论文中的应变平均值进行的相关分析表明，味觉调节与被认为反映乙醇强化或奖励（乙醇饮用、条件性位置偏好）的两种表型之间没有显着的遗传相关性。然而，高剂量的味觉调节与对乙醇引起的体温过低、旋转共济失调和急性戒断的敏感性之间存在显着的遗传相关性。品系平均值的数量性状位点 (QTL) 分析表明，味觉厌恶与九条染色体（1、2、3、4、6、7、9、11 和 17）上的遗传标记相关（p < 0.01）。这些 QTL 位于多个候选基因附近，包括编码多个不同乙酰胆碱受体亚基、6 个阿片受体和两个血清素受体（1B 和 1D）的基因。糖精偏好的 QTL 位于几条相同的染色体上（2、3、4、6 和 11）。其中两个糖精 QTL 与影响甜味或苦味刺激敏感性的候选基因重叠。总的来说，这些发现支持以下结论：多个基因影响乙醇诱导的条件性味觉厌恶。其中一些基因似乎影响味觉敏感性，而其他基因似乎介导对乙醇令人厌恶的药理作用的敏感性。
Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given l-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, ip). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes(1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the 6 opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.