LABORATORY MODELS OF COCAINE SELF ADMINISTRATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标： 目的1.在胸径基因座上对寻求可卡因依赖的非治疗志愿者进行基因分型。还将测量血浆DBH活性。 目的2.利用两种可卡因自身给药的人体实验室模型，确定双硫仑治疗对可卡因自我给药的影响。 假设一：我们预计大约三分之二的种群将具有C/C胸径基因，这与较高的胸径活动有关，大约三分之一的人口将具有C/T或T/T基因，这与中等(C/T)或低(T/T)胸径活动相关。这些估计是基于对非毒品使用人群的研究，在使用可卡因的人群中，胸径基因的分布可能是倾斜的。这项研究可能会提供这方面的进一步数据。对血浆DBH活性的测量也将允许根据实际酶活性进行分析。 假设2：我们预计双硫兰治疗将与减少可卡因的自我给药有关。拟议的研究结果将提供关于两种不同的可卡因自我给药实验室模型的预测价值的信息。如果这两个实验室模型中的一个或两个的结果与已公布的双硫仑临床试验的结果一致，则应进行旨在优化设计参数的进一步研究，以进一步开发这些方法。开发有效的实验室模型将极大地促进寻找更有效的可卡因依赖治疗方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS: AIM 1. To genotype non-treatment seeking cocaine-dependent volunteers at the DBH locus. Plasma DBH activity will also be measured. AIM 2. To determine the effects of treatment with disulfiram on cocaine self-administration using two human laboratory models of cocaine self-administration. HYPOTHESIS 1: We anticipate that about two-thirds of the population will have the C/C DBH genotype, which is associated with higher DBH activity, and about one-third of the population will have the C/T or T/T genotypes, which are associated with moderate (C/T) or low (T/T) DBH activity. These estimates are based on studies of non-drug using populations, and the distribution of DBH genotypes may be skewed in cocaine-using populations. This study may provide further data in this regard. Measurement of plasma DBH activity will also allow analysis based on actual enzyme activity. HYPOTHESIS 2: We anticipate that disulfiram treatment will be associated with reduced cocaine self-administration. Results of the proposed research will provide information about the predictive value of two different laboratory models of cocaine self-administration. If results from either or both of these laboratory models are congruent with outcomes from published clinical trials of disulfiram, then further research aimed at optimizing design parameters would be indicated to further develop these approaches. The development of valid laboratory models would greatly facilitate the search for more effective treatments for cocaine dependence.