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：
10.1097/00008571-199910000-00007
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发表时间：
1999-10
期刊：
影响因子：
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通讯作者：
Byron C. Jones;Lisa M. Tarantino;Lawrence A. Rodriguez;Cheryl L. Reed;G. Mcclearn;R. Plomin;V. Gene Erwin
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文献类型：
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作者：
Byron C. Jones;Lisa M. Tarantino;Lawrence A. Rodriguez;Cheryl L. Reed;G. Mcclearn;R. Plomin;V. Gene Erwin
我们最近在BxD/Ty重组近交系小鼠组中对可卡因对几种活动指标的影响进行了一项剂量 - 反应研究。动物在自动活动箱中进行为期2天的测试，第1天腹腔注射生理盐水，第2天腹腔注射可卡因，可卡因剂量为4种，分别是5、15、30或45毫克/千克。监测仪记录了总移动距离、在洞板中的鼻触次数、重复运动以及个体在靠近仪器中心所花费的时间。运动激活的剂量 - 反应曲线，即可卡因和生理盐水得分之间的差异，表明对于所有受试品系，得分在5 - 30毫克/千克范围内增加。除少数例外，45毫克/千克的运动活性并不显著高于30毫克/千克。重复运动得分显示出与运动活性相似的模式，并且鼻触次数往往随着可卡因剂量的增加而逐渐受到抑制。所有行为和所有剂量下的重组近交系品系平均分布呈现出连续的，而非离散的变化，从而为可卡因相关行为的多基因效应提供了证据。数量性状基因座（QTL）分析指出了几个与可卡因相关行为变化相关的染色体位置，其中一些与其他人所报道的QTL相同或相近。在不同组的动物中，测量了内侧前额叶皮质、尾状核 - 壳核、伏隔核和中脑腹侧的多巴胺D1和D2受体以及多巴胺摄取转运体的密度。在所有区域，所有测量结果都显示出与多基因影响一致的分布，并且与QTL相关。特别有趣的是我们在15号染色体上发现的一个大片段，它与多巴胺受体密度和可卡因相关行为有关。
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 D1, and D2 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.