Genetic correlation between the free-choice oral consumption of nicotine and alcohol in C57BL/6J x C3H/HeJ F2 intercross mice
Genetic correlation between the free-choice oral consumption of nicotine and alcohol in C57BL/6J x C3H/HeJ F2 intercross mice
复制标题
DOI：
10.1016/j.bbr.2004.06.010
复制
发表时间：
2005-02-10
影响因子：
2.7
通讯作者：
Stitzel, JA
中科院分区：
文献类型：
--
作者：
Li, XC;Karadsheh, MS;Stitzel, JA
先前的人类研究已经证明了酗酒和吸烟之间的高并发症。酒精和尼古丁依赖之间的这种共病可以部分归因于共同的遗传因素。在啮齿动物中，对酒精和尼古丁的行为和生理反应似乎也具有共同的遗传影响。本研究以C57 BL/6 x C3 H/HeJ F2杂交小鼠为研究对象，采用全升双瓶选择范式，研究了自由选择口服尼古丁与口服酒精摄入量之间的遗传相关性。对于所有浓度的尼古丁（25，50和100 mug/ml）和酒精（3，6和10%）测试，尼古丁消耗量与酒精消耗量显着相关。在测试的最高尼古丁浓度（100 μ g/ml）下的尼古丁消耗量与海马中[H-3]-野靛碱结合位点的数量（r = 0.307）和皮质中[I-125]-α-银环蛇毒素结合位点的数量（r = -0.328）显示出较低但显著的相关性。饮酒量与[H-3]-野靛碱或[I-125]-α-银环蛇毒素结合位点的数量之间没有显著相关性。烟碱受体α 4亚基基因Chrna 4的多态性显示出与雌性小鼠尼古丁消耗量和酒精消耗量显著相关的趋势，但与雄性小鼠无关。这些结果表明，共同的遗传因素影响小鼠的尼古丁和酒精消耗。然而，无论是[H-3]-野靛碱或[I-125]-α-银环蛇毒素结合烟碱受体表达的个体差异，还是Chrna 4的多态性，都不可能导致影响C57 BL/6 x C3 H/HeJ F2小鼠中这两种滥用药物消耗的遗传重叠。(C)2004 Elsevier B. V.保留所有权利。
Previous studies in humans have demonstrated a high co-morbidity between alcoholism and smoking. This co-morbidity between alcohol and nicotine dependence can be attributed, in part, to common genetic factors. In rodents, behavioral and physiological responses to alcohol and nicotine also appear to share common genetic influences. In this report, the genetic correlation between free-choice oral nicotine and oral alcohol consumption was evaluated using all ascending two-bottle choice paradigm in C57BL/6 x C3H/HeJ F2 intercross mice. For all concentrations of nicotine (25, 50, and 100 mug/ml) and alcohol (3, 6, and 10%) tested, nicotine consumption was significantly correlated with alcohol consumption. Nicotine consumption at the highest nicotine concentration tested (100 mug/ml) showed low, but significant, correlations with the number of [H-3]-cytisine binding sites in the hippocampus (r = 0.307) and the number of ([I-125]-alpha-bungarotoxin binding sites in the cortex r = -0.328). No significant correlations between alcohol consumption and the number of either [H-3]-cytisine or [I-125]-alpha-bungarotoxin binding sites was observed. A polymorphism in the nicotinic receptor alpha4 subunit gene, Chrna4, showed a trend with nicotine consumption and a significant association with alcohol consumption ill female but not male mice. These results indicate that common genetic factors influence nicotine and alcohol consumption in mice. However, neither individual differences in the expression of [H-3]-cytisine or [I-125]-alpha-bungarotoxin binding nicotinic receptors nor the polymorphism in Chrna4 likely contribute to the genetic overlap that influences the consumption of both of these drugs of abuse in C57BL/6 x C3H/HeJ F2 mice. (C) 2004 Elsevier B.V. All rights reserved.