Biobehavioral Studies of Opioid Drug Seeking Behavior

描述（由申请人提供）：学习理解，预测和控制药物寻求行为对公共卫生很重要。在这项修订的五年R 01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通过三种类型的环境因素减少-补充阿片类药物的可用性，药物价格和非药物替代品。 将使用选择（金钱与氢吗啡酮[HYD]）渐进比率任务来测量阿片类药物寻求。 受试者将维持丁丙诺啡（以控制生理状态），并在住院条件下进行研究（以控制外源性药物使用）。拟议的研究具有重要意义，原因有几个。第一，环境条件对寻求毒品的影响可能在毒品类别、个人和环境中发挥作用，因此具有普遍重要性。其中一个因素-药物的可获得性-已被断言会影响药物寻求，但很少有对这一假设进行严格控制的检验。其次，大多数关于药物寻求和行为经济需求（即在不同药物价格和非药物替代品的背景下的选择）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以往研究结果的普遍性。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证据。研究1将确定是否有会前机会采取“免费”（不劳而获）补充HYD，即，开放的经济环境影响了反应相依混合动力汽车的累进比例寻求。还将检查加强剂剂量和固定比例值对HYD寻求的影响。 我们预测，相对于封闭经济（没有补充HYD），增加对响应相关HYD剂量的补充将减少HYD寻求（减少断点并增加弹性）。研究2将调查治疗后补充HYD的可用性（0%，50%或100%的响应-视情况而定的HYD补充剂剂量）和替代货币的大小（工资率：2美元[重复研究1]与每次试验4美元）是否影响药物寻求。 我们预测，增加HYD补充剂和更高数量的金钱替代品将减少HYD寻求。研究3将探讨是否模拟就业，失业和惩罚差异影响HYD寻求。就业将是研究2中的高量级货币替代方案（4美元/试验，同时使用药物）;失业将提供同时使用药物的机会，但没有货币替代方案;惩罚条件将排除货币收入，并为选择同时使用药物的每次试验产生4美元的损失。将在封闭和会后开放经济体中对这些条件进行评估（部分重复研究2）。我们预测，就业和惩罚将增加HYD的需求弹性相对于失业，这些影响将是更大的开放比封闭的经济条件下。

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.