Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Department of Human and Molecular Genetics, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
J Psychopharmacol. 2024 Nov;38(11):1007-1015. doi: 10.1177/02698811241269691. Epub 2024 Aug 13.
Nicotine is largely responsible for the initiation and maintenance of tobacco dependence and contributes to a global health problem.
This study characterizes nicotine oral consumption and preference in male and female mice of several Diversity Outbred (DO) founder strains: C57BL/6J, A/J, 129S1/SvImJ, PWK/PhJ, NOD/ShiLtJ, and CAST/EiJ. It assesses the impact of nicotine concentration on intake and preference, the potential interaction of strain with sex, and estimates the degree of heritable variation in nicotine consumption.
Two-bottle choice oral self-administration paradigm was used to assess nicotine intake, nicotine preference, and total fluid intake in male and female mice of each strain in a concentration-response manner. A conditioned place preference (CPP) test was performed to evaluate the rewarding and aversive effects of nicotine in certain strains after systemic administration of the drug.
The highest nicotine-consuming strain was found to be 129S1/SvlmJ, and the lowest nicotine-consuming strain was A/J. Strain differences in nicotine intake were not due to differences in bitter and sweet tastes as shown in the saccharine and quinine two-bottle choice tests. A/J strain showed no significant CPP for nicotine while the 129S1/SvImJ strain showed a significant CPP for nicotine and a higher preference when compared to the C57BL/6J strain. Heritability estimates of nicotine intake were sex dependent and concentration dependent.
Data support that nicotine consumption patterns are heritable with an influence of genotype in a voluntary oral self-administration paradigm. Results pave the way for future studies with the highly recombinant DO mice that might lead to the identification of novel genetic loci and genes influencing nicotine consumption.
尼古丁在很大程度上导致了烟草依赖的开始和维持，并促成了一个全球性的健康问题。
本研究描述了几种多样性远交（DO）创始品系（包括 C57BL/6J、A/J、129S1/SvImJ、PWK/PhJ、NOD/ShiLtJ 和 CAST/EiJ）雄性和雌性小鼠对尼古丁的口服消耗和偏好。评估了尼古丁浓度对摄入量和偏好的影响，评估了品系与性别的潜在相互作用，并估计了尼古丁消耗的可遗传性变异程度。
采用双瓶选择口服自我给药范式，以浓度反应方式评估每个品系雄性和雌性小鼠的尼古丁摄入量、尼古丁偏好和总液体摄入量。进行条件位置偏好（CPP）测试，以评估在系统给予药物后某些品系中尼古丁的奖赏和厌恶作用。
发现 129S1/SvlmJ 是消耗尼古丁最多的品系，而 A/J 是消耗尼古丁最少的品系。尼古丁摄入量的品系差异不是由于在蔗糖和奎宁双瓶选择测试中苦味和甜味的差异造成的。A/J 品系对尼古丁没有明显的 CPP，而 129S1/SvImJ 品系对尼古丁有明显的 CPP，与 C57BL/6J 品系相比，对尼古丁的偏好更高。尼古丁摄入量的遗传力估计值依赖于性别和浓度。
数据表明，在自愿口服自我给药范式中，尼古丁的消耗模式是可遗传的，并且受到基因型的影响。结果为未来使用高度重组的 DO 小鼠进行研究铺平了道路，这可能导致鉴定影响尼古丁消耗的新遗传位点和基因。
