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COCAINE, CORTICOSTERONE AND EMOTIONAL BEHAVIOR

可卡因、皮质酮和情绪行为

基本信息

批准号：
2881762
负责人：
JEFFREY B ROSEN
金额：
$ 7.5万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-07-01 至 2002-06-30
项目状态：
已结题

项目摘要

Cocaine is one of the most potent reinforcers known; both humans and animals will crave and expend much energy to acquire these drugs. However, one of the many negative consequences of repeated cocaine use in humans is the development of panic and anxiety following cocaine withdrawal. Thus, cocaine has pleasurable, reinforcing properties, as well as anxiety-inducing effects. Although dopamine is known to be an important mediator of cocaine, stress hormones, such as corticosteroids, are thought to play a critical but paradoxical role in both the reinforcing and anxiety-inducing effects of cocaine. The goal of this proposal is to investigate the role of corticosteroids in the long-lasting anxiolytic (pleasurable) and anxiogenic properties of cocaine in rats. A paradigm that measures both long-lasting anxiolytic and anxiogenic effects of prior repeated cocaine administration by a single behavioral response, the acoustic startle reflex, will be described. Depending on the experience, both pleasurable and fearful states can be measured by the acoustic startle response. Startle decreases in an environment where the rats have previously been positively reinforced, and conversely, is increased following fear conditioning. The paradigm will be used to test the hypothesis that corticosteroids are critical for both the anxiolytic and anxiogenic effects of repeated cocaine following withdrawal. Adrenalecomized rats will be given repeated administration of cocaine, and then following a withdrawal period, will be tested for increased in pleasure and fear by measuring amplitude of the startle reflex. Corticosterone will also be given in an attempt to reverse the effects of adrenalectomy. In addition, pharmacological inhibition of corticosterone production will also be evaluated. The results will indicate whether corticosteroids are necessary for both the pleasurable and anxiety-inducing effects of cocaine, or for only one of the effects. The study will have important implications for understanding the environmental and behavioral control over the pleasurable and anxiogenic properties of cocaine and whether stress hormones regulate both of these properties or regulate cocaine-related pleasure and anxiety differentially. The outcome of the experiments should have ramifications for understanding drug abuse and relapse, and development of treatment and prevention strategies.

可卡因是已知的最有效的兴奋剂之一;人类和动物都会渴望并花费大量精力来获得这些药物。然而，人类重复使用可卡因的许多负面后果之一是可卡因戒断后恐慌和焦虑的发展。因此，可卡因具有令人愉快的，增强的特性，以及焦虑诱导作用。虽然已知多巴胺是可卡因的重要介质，但应激激素（如皮质类固醇）被认为在可卡因的强化和焦虑诱导作用中起着关键但矛盾的作用。本研究的目的是研究皮质类固醇在大鼠可卡因的持久抗焦虑（愉悦）和致焦虑特性中的作用。一个范例，测量持久的抗焦虑和焦虑的影响，以前重复可卡因管理的一个单一的行为反应，声惊吓反射，将被描述。根据不同的经验，愉快和恐惧的状态都可以通过声音惊吓反应来测量。在老鼠先前被积极强化的环境中，惊吓减少，相反，在恐惧条件反射后增加。该范例将用于检验皮质类固醇对戒断后重复可卡因的抗焦虑和致焦虑作用至关重要的假设。将给予肾上腺皮质化的大鼠重复施用可卡因，然后在戒断期后，通过测量惊吓反射的幅度来测试快乐和恐惧的增加。还将给予皮质酮以试图逆转肾上腺切除术的影响。此外，还将评价皮质酮产生的药理学抑制。结果将表明皮质类固醇是否是可卡因的愉悦和焦虑诱导作用所必需的，或者仅是其中一种作用。这项研究将对理解可卡因的愉悦和焦虑特性的环境和行为控制以及压力激素是否调节这两种特性或差异调节可卡因相关的愉悦和焦虑具有重要意义。实验的结果应当对理解药物滥用和复吸以及制定治疗和预防战略产生影响。