Doyle Glenn A, Furlong Patrick J, Schwebel Candice L, Smith George G, Lohoff Falk W, Buono Russell J, Berrettini Wade H, Ferraro Thomas N
Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA 19104, USA.
Neuropsychopharmacology. 2008 Nov;33(12):2801-9. doi: 10.1038/npp.2008.14. Epub 2008 Feb 20.
C57BL/6J (B6) and DBA/2J (D2) mice differ in behaviors related to substance abuse, including voluntary morphine consumption and preference in a two-bottle choice paradigm. Two major quantitative trait loci (QTL) for morphine consumption and preference exist between these strains on chromosomes (Chrs.) 6 and 10 when the two-bottle choice involves morphine in saccharin vs quinine in saccharin. Here, we report the refinement of the Chr. 10 QTL in subcongenic strains of D2.B6-Mop2 congenic mice described previously. With these subcongenic mouse strains, we have divided the introgressed region of Chr. 10 containing the QTL gene(s) into two segments, one between the acromere and Stxbp5 (in D2.B6-Mop2-P1 mice) and the other between marker D10Mit211 and marker D10Mit51 (in D2.B6-Mop2-D1 mice). We find that, similar to B6 mice, the D2.B6-Mop2-P1 congenic mice exhibit a strong preference for morphine over quinine, whereas D2.B6-Mop2-D1 congenic mice avoid morphine (similar to D2 mice). We have also created a line of double congenic mice, B6.D2-Mop2.Qui, which contains both Chr. 10 and Chr. 6 QTL. We find that they are intermediate in their morphine preference scores when compared with B6 and D2 animals. Overall, these data suggest that the gene(s) involved in morphine preference in the morphine-quinine two-bottle choice paradigm are contained within the proximal region of Chr. 10 (which harbors Oprm1) between the acromere and Stxbp5, as well as on distal Chr. 6 between marker D6Mit10 and the telomere.
C57BL/6J（B6）小鼠和DBA/2J（D2）小鼠在与药物滥用相关的行为上存在差异，包括在双瓶选择范式中的自愿吗啡摄入量和偏好。当双瓶选择涉及糖精中的吗啡与糖精中的奎宁时，这两个品系在6号和10号染色体上存在两个与吗啡摄入量和偏好相关的主要数量性状位点（QTL）。在此，我们报告了先前描述的D2.B6-Mop2同源基因小鼠亚同源基因系中10号染色体QTL的精细化。利用这些亚同源基因小鼠品系，我们已将包含QTL基因的10号染色体渐渗区域分为两个区段，一个在着丝粒和Stxbp5之间（在D2.B6-Mop2-P1小鼠中），另一个在标记D10Mit211和标记D10Mit51之间（在D2.B6-Mop2-D1小鼠中）。我们发现，与B6小鼠相似，D2.B6-Mop2-P1同源基因小鼠对吗啡的偏好明显高于奎宁，而D2.B6-Mop2-D1同源基因小鼠则回避吗啡（与D2小鼠相似）。我们还创建了一个双同源基因小鼠品系B6.D2-Mop2.Qui，其同时包含10号和6号染色体QTL。我们发现，与B6和D2动物相比，它们的吗啡偏好得分处于中间水平。总体而言，这些数据表明，在吗啡 - 奎宁双瓶选择范式中参与吗啡偏好的基因位于10号染色体近端区域（包含Oprm1）着丝粒和Stxbp5之间，以及6号染色体远端标记D6Mit10和端粒之间。
