Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry
Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry
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DOI：
10.1097/01213011-199910000-00007
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发表时间：
1999-10-01
期刊：
影响因子：
--
通讯作者：
Erwin, VG
中科院分区：
文献类型：
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作者：
Jones, BC;Tarantino, LM;Erwin, VG
我们最近进行了一项剂量反应研究，研究可卡因对BxD/Ty重组近交系小鼠几项活性指标的影响。动物在一个自动活动室中进行了为期2天的试验，第1天口服生理盐水，第2天口服可卡因，剂量为5、15、30或45 mg kg（-1）。监测器记录了行走的总距离，在孔板上的鼻戳，重复的动作和个人在接近设备中心的时间。运动激活的剂量-反应曲线，即可卡因和生理盐水评分的差异，显示所有测试菌株的得分都增加了5-30 mg kg(-1)，除了少数例外，45 mg kg（-1）的运动活动不显著高于30 mg kg（-1）。重复运动得分显示出与运动活动相似的模式，鼻突倾向于随着可卡因剂量的增加而逐渐受到抑制。在所有剂量下，所有行为的重组自交系平均分布表现出连续而非离散的变化，从而提供了多基因对可卡因相关行为影响的证据。定量性状位点（QTL）分析指出了几个与可卡因相关行为变异相关的染色体位置，其中一些与其他人报道的QTL相同或接近。在不同的动物组中，测量了多巴胺D-1和D-2受体和多巴胺摄取转运体在内侧前额叶皮层、尾状壳核、伏隔核和中脑腹侧的密度。在所有区域，所有测量都显示了与多基因影响一致的分布，并与QTL相关。特别有趣的是，我们在第15号染色体上发现了一个大片段，它与多巴胺受体密度和可卡因相关行为有关。药物遗传学(C) 1999。
We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg(-1). The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg(-1), With few exceptions, locomotor activity at 45 mg kg(-1) was not significantly higher than that at 30 mg kg(-1). Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D-1, and D-2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL, Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours. Pharmacogenetics 9:607-617 (C) 1999 Lippincott Williams & Wilkins.