Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line
Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line
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DOI：
10.3389/fgene.2012.00126
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发表时间：
2012-01-01
影响因子：
3.7
通讯作者：
Palmer, Abraham A.
中科院分区：
文献类型：
--
作者：
Bryant, Camron D.;Kole, Loren A.;Palmer, Abraham A.
条件性位置偏爱（CPP）试验常用于评价小鼠滥用药物的奖励特性。尽管CPP在转基因和基因敲除实验中得到广泛应用，但很少有使用CPP来识别有助于药物奖励的新基因的正向遗传学研究。在这项研究中，我们测试了LG/J和SM/J自交系和F-45/F-46高级互交系（AIL）的10个家庭的父母/后代的甲基苯丙胺诱导的CPP（MA-CPP），每周一次，持续2周。LG/J和SM/J小鼠均表现出显著的MA-CPP，这在两个品系之间没有显著差异。此外，LG/J小鼠表现出显着减少急性MA诱导的运动活动，以及随后的MA注射后的运动致敏。分离LG/J和SM/J等位基因的AIL小鼠（N = 105）也表现出显著的MA-CPP，其在训练的第一周和第二周之间的幅度相等。重要的是，AIL小鼠中的MA-CPP与无药物或MA诱导的运动活动无关，表明MA-CPP不受测试阶段活动的混淆，并暗示MA-CPP在遗传上与急性精神敏感性不同。我们估计的遗传力的MA-CPP和运动表型使用中亲后代回归和最大似然估计来自AIL家系的亲属关系系数。MA-CPP的遗传力估计值较低（0-0.21）且可变（SE = 0-0.33），这反映了我们仅使用10个中亲后代观察值估计遗传力的能力较差。总之，我们在AIL小鼠中建立了MA-CPP的短期方案，可以揭示对MA奖励重要的LG/J和SM/J等位基因。使用高度重组的遗传群体，如AIL，应有助于识别这些基因，并可能对理解人类精神兴奋剂滥用产生影响。
The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F-45/F-46 advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.