Gill Kathryn J, Boyle Alan E
McGill University Health Centre Research Institute, Psychiatry Department, McGill University, Montreal, Quebec, Canada.
Pharmacogenetics. 2003 Jun;13(6):329-38. doi: 10.1097/00008571-200306000-00004.
Individual differences in the psychomotor stimulant effects of cocaine are influenced by genetic factors. Several quantitative trait loci (QTL) have been identified for cocaine-induced locomotor activation using the AXB/BXA recombinant inbred series of strains derived from the A/J (A) and C57BL/6J (B6). The aim of the present study was to conduct an independent analysis of cocaine-induced activation in the AcB/BcA recombinant congenic strains. The AcB/BcA RC series consists of 37 inbred strains derived from reciprocal backcrosses between the A and B6, followed by systematic inbreeding. Locomotor activity was measured in a computerized open-field apparatus following intraperitoneal administration of saline and cocaine (20 mg/kg). Linkage maps constructed with 625 informative microsatellite markers were used to identify chromosomal regions associated with cocaine difference scores. Significant (P < 0.00001) regions were identified on chromosomes 1 (13-25.7 and 36.9-58.5 cM), 5 (1-28 and 84-86 cM), 6 (7-26.35 cM), 7 (9.4-27.8 cM), 9 (9-28 cM), 13 (21-37 cM), 16 (36-66 cM), 17 (22.5-24.5 cM) and 18 (45-48 cM). Multiple regression analysis demonstrated that a subset of four markers, including D5Mit182 (24 cM), D5Mit409 (84 cM), D7Mit83 (26.5 cM) and D13Mit54 (35 cM), accounted for 90% of the genetic variance in cocaine difference scores. The results of the present study provide confirmation for a number of QTL on chromosomes 1, 5, 6, 9, 16 and 17 which were previously identified in the recombinant inbred AXB/BXA and BXD strains that share a common B6 ancestor.
可卡因精神运动性兴奋作用的个体差异受遗传因素影响。利用源自A/J（A）和C57BL/6J（B6）的AXB/BXA重组近交系，已鉴定出多个与可卡因诱导的运动激活相关的数量性状基因座（QTL）。本研究的目的是对AcB/BcA重组同类系中可卡因诱导的激活进行独立分析。AcB/BcA重组同类系由37个近交系组成，这些近交系源自A和B6之间的相互回交，随后进行系统的近亲繁殖。在腹腔注射生理盐水和可卡因（20mg/kg）后，使用计算机化的旷场装置测量运动活性。用构建的包含625个信息性微卫星标记的连锁图谱来鉴定与可卡因差异评分相关的染色体区域。在染色体1（13 - 25.7和36.9 - 58.5cM）、5（1 - 28和84 - 86cM）、6（7 - 26.35cM）、7（9.4 - 27.8cM）、9（9 - 28cM）、13（21 - 37cM）、16（36 - 66cM）、17（22.5 - 24.5cM）和18（45 - 48cM）上鉴定出显著（P < 0.00001）区域。多元回归分析表明，包括D5Mit182（24cM）、D5Mit409（84cM）、D7Mit83（26.5cM）和D13Mit54（35cM）在内的四个标记子集占可卡因差异评分遗传变异的90%。本研究结果证实了先前在具有共同B6祖先的重组近交AXB/BXA和BXD品系中鉴定出的位于染色体1、5、6、9、16和17上的多个QTL。
