Social & Environmental Influences on Opioid Sensitivity

描述（由申请人提供）：阿片类药物滥用研究的一个主要组成部分是确定导致受试者人群中阿片类药物敏感性差异的各种生物学、药理学和环境因素。对阿片类药物敏感性产生强烈影响的一组因素是受试者的社会和环境住房条件。事实上，许多研究已经报道了不同安置受试者对阿片类药物的抗伤害性，运动和奖励作用的敏感性差异。拟议研究项目的目的是对造成这些差异的因素进行系统的检查。预期在介导差异安置受试者之间阿片样物质敏感性差异中起重要作用的一个因素是阿片样物质的内在功效（即，其在结合到其受体位点后引发细胞应答的能力）。以前的研究考察了社会和环境住房条件与阿片类药物敏感性之间的关系，通常在行为测试期间完全依赖于高效μ阿片类药物。这是一个潜在的重大问题，考虑到最近的证据表明，当测试疗效较低的阿片类药物时，许多受试者人群之间的阿片类药物敏感性差异最为明显。在拟议的研究项目中，将通过测试在μ受体上具有一系列内在功效的阿片类药物，来检查不同圈养受试者之间对μ阿片类药物的抗伤害感受、运动和奖励效应的敏感性差异。拟议的实验旨在确定受试人群之间阿片类药物敏感性差异最明显的条件，并提供介导这些差异的潜在受体机制的线索。

DESCRIPTION (provided by applicant): A major component of opioid abuse research involves identifying the various biological, pharmacological and environmental factors that contribute to differences in opioid sensitivity across subject populations. One set of factors that exerts a strong influence on sensitivity to the effects of opioids is the social and environmental housing conditions of the subject. Indeed, numerous studies have reported differences in sensitivity to the antinociceptive, locomotor, and rewarding effects of opioids across differentially housed subjects. The purpose of the proposed research project is to perform a systematic examination of the factors contributing to these differences. One factor expected to play a large role in mediating differences in opioid sensitivity between differentially housed subjects is the intrinsic efficacy of the opioid (i.e., its ability to initiate a cellular response after binding to its receptor site). Previous studies examining the relationship between social and environmental housing conditions and opioid sensitivity have typically relied exclusively on high efficacy mu opioids during behavioral testing. This is a potentially significant issue considering recent evidence indicating that differences in opioid sensitivity between many subject populations are most apparent when lower efficacy opioids are tested. In the proposed research project, differences in sensitivity to the antinociceptive, locomotor, and rewarding effects of mu opioids between differentially housed subjects will be examined by testing opioids possessing a range of intrinsic efficacy at the mu receptor. The proposed experiments are designed to identify the conditions under which differences in opioid sensitivity between subject populations are most apparent and provide clues as to the underlying receptor mechanisms mediating these differences.