Biobehavioral Studies of Opioid Drug Seeking Behavior

描述(由申请者提供)：学习了解、预测和控制寻求毒品行为对公众健康很重要。在这份修订后的五年R01申请中描述的三项研究将调查海洛因依赖志愿者寻求阿片类药物的程度可以被三种类型的环境因素--补充阿片类药物的可获得性、药品价格和非药物替代品--减少的程度。选择(金钱与氢吗啡酮[HYD])累进比率任务将被用来衡量阿片类药物寻求。参与者将继续服用丁丙诺啡(以控制生理状态)，并在住院条件下进行研究(以控制外来药物的使用)。拟议中的研究具有重要意义，原因有几个。首先，环境条件对寻求毒品的影响可能跨越毒品类别、个人和环境，因此具有普遍重要性。一个这样的因素--药物的可获得性--被断言会影响药物寻求，但很少有对这一假设进行良好控制的测试。其次，大多数关于寻求毒品和行为经济需求(即在不同药品价格和非药品替代情况下的选择)的人类研究都集中在吸烟上。因此，拟议的研究将有助于评估先前研究结果的一般性。第三，研究结果将提高对药物依赖机制的理解，并为治疗和政策提供经验驱动的证据。研究1将确定会前参加“免费”(不劳而获)补充HYD的机会，即开放经济，是否影响响应应急HYD的累进比率寻求。此外，还将考察增强剂剂量和固定比例值对HYD寻找的影响。我们预测，与封闭经济(不补充HYD)相比，增加反应应急HYD剂量的补充将减少HYD寻求(减少断点和增加弹性)。研究2将调查会后补充HYD的可获得性(反应应急HYD增强剂剂量的0%、50%或100%)和替代货币的大小(工资率：2美元[研究1的重复]与每个试验4美元)是否影响药物寻求。我们预测，增加HYD补充剂和更高金额的货币替代品将减少HYD的寻求。研究三将考察模拟就业、失业和惩罚是否会对海德寻求产生不同的影响。就业将是研究2的高金额金钱选择(同时使用药物的试验每项4美元)；失业将提供同时使用药物的机会，但没有金钱替代；惩罚条件将排除金钱收入，并为选择同时使用药物的每一次试验产生4美元的损失。将在封闭式经济体和会后开放型经济体中对这些条件进行评估(研究2的部分复制)。我们预测，就业和惩罚将增加相对于失业的需求弹性，并且在开放经济条件下，这些影响将比封闭经济条件下更大。

DESCRIPTION (provided by applicant): Learning to understand, predict and control drug-seeking behavior is important to public health. Three studies described in this revised five-year R01 application will investigate the extent to which opioid drug seeking by heroin dependent volunteers can be reduced by three types of environmental factors--supplemental opioid availability, drug price, and non-drug alternatives. A choice (money versus hydromorphone [HYD]) progressive ratio task will be used to measure opioid drug seeking. Participants will be maintained on buprenorphine (to control physiological state) and studied under inpatient conditions (to control extraneous drug use). The proposed studies are significant for several reasons. First, the effects of environmental conditions on drug seeking may operate across drug classes, individuals and settings and are therefore of general importance. One such factor--drug availability--has been asserted to influence drug seeking, but there are few well-controlled tests of this hypothesis. Second, most human studies of drug seeking and behavioral economic demand (i.e. choice in the context of varying drug price and non-drug alternatives) have focused on cigarette smoking. Therefore, the proposed studies will help to assess the generality of previous findings. Third, findings from the studies will improve understanding of drug dependence mechanisms and provide empirically driven evidence for treatment and policy. Study 1 will determine whether pre-session opportunity to take "free" (unearned) supplemental HYD, i.e., an open economy, influences progressive ratio seeking of response-contingent HYD. Effects of reinforcer dose and fixed ratio values on HYD seeking will also be examined. We predict that increasing supplements to the response-contingent HYD dose will decrease HYD seeking (decrease breakpoint and increase elasticity), relative to a closed economy (no supplemental HYD). Study 2 will investigate whether post-session supplemental HYD availability (0%, 50% or 100% of the response-contingent HYD reinforcer dose) and magnitude of alternative money (wage rate: $2 [replication of Study 1] versus $4 per trial) influence drug seeking. We predict that increasing HYD supplements and the higher-magnitude money alternative will reduce HYD seeking. Study 3 will investigate whether simulated employment, unemployment and punishment differentially affect HYD seeking. Employment will be the high-magnitude money alternative from Study 2 ($4/trial with concurrent drug); Unemployment will provide concurrent drug access but no money alternative; and the Punishment condition will preclude money earnings and produce a loss of $4 for each trial that concurrent drug is chosen. These conditions will be evaluated in both closed and post-session open economies (partial replication of Study 2). We predict that employment and punishment will increase HYD demand elasticity relative to unemployment, and that these effects will be greater under open than closed economic conditions.