Resurgence of Punishment-Suppressed Cocaine Seeking

受惩罚抑制的可卡因寻觅活动死灰复燃

基本信息

批准号：
8837903
负责人：
Timothy A Shahan
金额：
$ 20.83万
依托单位：
UTAH STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2017-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Relapse following periods of abstinence is a defining feature of drug addiction. In standard animal models of relapse, an operant response (e.g., lever press) is reinforced by drug delivery. Drug seeking is then extinguished by withholding the drug, and relapse is induced by exposure to drugs, drug-cues/contexts, or stress. Drug and non-drug reinforcers are known to interact in the control of behavior, and availability of alternative non-drug reinforcers decreases drug taking. Behavioral interventions arranging non-drug reinforcers have been very successful, but when such treatment ends, the discontinuation of alternative reinforcement is often associated with relapse. In addition, some potentially stress-related sources of relapse (e.g., changes in familial or vocational circumstances) might be characterized as involving the loss of alternative non-drug reinforcers. Standard animal models of relapse do not examine such relapse induced by loss of alternative non-drug reinforcement. Our laboratory has developed the resurgence model in which extinguished drug seeking increases (i.e., relapses) when an alternative source of non- drug reinforcement is subsequently removed. However, a long-standing criticism of animal models of relapse, including the resurgence paradigm, is that they achieve suppression of drug seeking by extinguishing drug seeking prior to relapse testing. The concern with the use of extinction is that cessation of drug seeking by humans is clearly not the result of extinction of drug seeking. Instead, considerable evidence suggests that the experience of negative consequences as a result of drug use is a contributing factor. The goal of this R21 Exploratory/Developmental grant is to develop a version of the resurgence model to examine relapse induced by loss of alternative reinforcement following suppression of cocaine seeking with negative consequences, rather than extinction. The project addresses a long-standing barrier to progress in the field resulting from the use of extinction as the means to suppress drug- seeking prior to relapse. By developing a version of the resurgence procedure using negative consequences to suppress drug seeking, the proposed research could result in a more appropriate model for examining the behavioral and neurobiological mechanisms of relapse induced by loss of non-drug reinforcement.

描述（申请人提供）：禁欲之后的复发是药物成瘾的定义特征。在标准的复发动物模型中，药物输送的操作反应（例如，杠杆出版社）得到了加强。然后，通过扣留药物来熄灭药物，并通过暴露于药物，药物/情况或压力来引起复发。已知药物和非药物增强剂在行为的控制中相互作用，替代非药物增强剂的可用性会减少药物服用。布置非药物增强剂的行为干预措施非常成功，但是当这种治疗结束时，替代增强的停用通常与复发有关。此外，某些潜在的与压力相关的复发来源（例如，家庭或职业状况的变化）可能被认为是涉及替代性非药水增强剂的丧失。复发的标准动物模型不会检查丢失替代非药物增强剂引起的复发。我们的实验室已经开发了复兴模型，在该模型中，当替代非药物加固的替代来源被删除时，寻求灭绝的药物增加（即复发）。但是，人们对包括复发范式在内的动物复发模型的长期批评是，它们通过在复发测试之前熄灭毒品来实现抑制药物寻求药物的抑制。使用灭绝的关注在于，人类寻求药物的停止显然不是灭绝毒品的结果。取而代之的是，大量证据表明，由于吸毒而导致负面后果的经历是一个促成因素。 R21探索性/发展赠款的目的是开发一种复发模型的版本，以检查在抑制可卡因寻求可卡因后因负面后果而不是灭绝而引起的替代加固引起的复发。该项目解决了由于使用灭绝作为在复发之前抑制吸毒的手段而导致的现场进展的长期障碍。通过使用负面后果来抑制药物寻求药物的复兴程序，这项研究可能会导致更合适的模型，以检查因丢失非药物加固而引起的复发的行为和神经生物学机制。