NEURAL MECHANISMS OF DRUG SEEKING BEHAVIOR

寻药行为的神经机制

• 批准号: 2014111
• 负责人: Janet L Neisewander
• 金额: $ 21.49万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-10 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2014111
• 关键词: amygdala; behavior; behavioral /social science research tag; cocaine; cues; dopamine agonists; drug addiction; drug withdrawal; ethology; imipramine; laboratory rat; microdialysis; neurochemistry; nucleus accumbens; operant conditionings; psychological models; reinforcer; relapse /recurrence; self medication

DESCRIPTION: (Applicant's Abstract) Measures of drug-seeking behavior in animals provide models that can be used to screen potential treatments for drug craving and relapse in humans and to study the neural mechanisms involved. These measures include operant responding for drug when it is no longer available (i.e., extinction) and reinstatement of responding either by administration of drug or presentation of drug-associated cues. The objective of the proposed research is to examine the role of monoamine (MA) systems in cocaine-seeking behavior using the extinction/reinstatement model. Animals trained to lever press for food will be trained to self-administer cocaine or will receive yoked administration of saline. After responding has been established, they will be given 14 daily 3-hr training sessions, followed by a final 12-hr "binge" session. Later, drug-seeking behavior, as well as MA overflow in the nucleus accumbens and amygdala, will be assessed in 3 test phases: phase 1 will assess operant responding during extinction; phase 2 will assess reinstatement of responding by presentation of cocaine-associated cues; phase 3 will assess reinstatement of responding following a cocaine injection. The following day, food-seeking behavior will be examined to determine whether changes observed previously are specific to drug-seeking. The first experiment will examine the relationship between changes in drug-seeking behavior and MA overflow during cocaine withdrawal in separate groups of animals tested 6 hr, 30 hr, 7 or 28 days after the last self-administration session. Next, the effect of chronic treatment with desmethylimipramine (DMI), a MA reuptake inhibitor with some anti-craving efficacy, on drug-seeking behavior and MA overflow will be investigated. MA receptor density will also be assayed post-mortem. It is hypothesized that cocaine withdrawal will produce a time-dependent increase in drug-seeking behavior that will correlate with neurochemical changes in MA systems, and that DMI treatment during withdrawal will attenuate drug-seeking behavior and reverse the neurochemical changes. Characterizing time-dependent changes in drug-seeking behavior and MA systems will provide a better understanding of cocaine withdrawal and relapse, and may provide insight into the neural mechanisms of drug-seeking behavior. This information is crucial for developing pharmacologic treatments for cocaine craving and relapse. The last experiments will investigate the hypothesis that the dopamine D3-- preferring agonist 7-OH-DPAT attenuates drug-seeking behavior. If confirmed, the findings would suggest a new pharmacologic treatment strategy for cocaine dependence.

描述：（申请人的摘要） 动物中寻求毒品行为的度量提供了可以使用的模型 筛选人类渴望和复发的潜在治疗方法 研究涉及的神经机制。 这些措施包括操作员 当药物不再可用时（即灭绝）和 恢复通过药物或呈递的响应 与药物相关的提示。 拟议研究的目的是 使用单胺（MA）系统在使用可卡因寻求行为中的作用 灭绝/恢复模型。 受过训练的动物，以抢购食物 将接受自我管理可卡因的培训或将受到训练 盐水给药。 建立响应后，他们将 每天进行14次3小时培训课程，然后进行最后的12小时“狂欢” 会议。 后来，寻求毒品的行为以及MA溢出 伏隔核和杏仁核将在3个测试阶段进行评估：第1阶段 将评估灭绝过程中的作战者；第二阶段将评估 通过出现可卡因相关线索来恢复响应； 第三阶段将评估可卡因后响应的恢复 注射。 第二天，将检查寻求食物的行为 确定先前观察到的变化是否特定于寻求药物。 第一个实验将检查变化之间的关系 在可卡因撤离期间，寻求毒品的行为和MA溢出 最后一次测试了6个小时，30小时，7或28天的动物。 自我管理会议。 接下来，与 Desmethylipramine（DMI），一种抗抗药性的MA再摄取抑制剂 将研究对毒品行为和MA溢出的功效。 马 受体密度也将在验尸后进行测定。 假设 可卡因的戒断将产生时间依赖于毒品的增加 与MA系统中神经化学变化相关的行为， 退出期间的DMI治疗将减弱寻求毒品的行为 并扭转神经化学的变化。 表征时间依赖性 寻求毒品行为和MA系统的变化将提供更好的 了解可卡因戒断和复发，并可能提供洞察力 进入寻求毒品行为的神经机制。 此信息是 对于开发可卡因渴望和 复发。 最后一个实验将研究以下假设 多巴胺D3-偏爱激动剂7-OH-DPAT会减弱寻求药物的行为。 如果得到确认，这些发现将提出新的药物治疗 可卡因依赖的策略。