COCAINE, CORTICOSTERONE AND EMOTIONAL BEHAVIOR

可卡因是已知的最有效的增强剂之一；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，人类反复使用可卡因的许多负面后果之一是在可卡因戒断后出现恐慌和焦虑。因此，可卡因具有令人愉悦、强化的特性，以及引发焦虑的效果。虽然已知多巴胺是可卡因的重要媒介，但应激激素，如皮质类固醇，被认为在可卡因的强化和引发焦虑的作用中发挥着关键但矛盾的作用。这项建议的目的是研究皮质类固醇在可卡因对大鼠的持久抗焦虑(愉悦)和致焦虑特性中的作用。将描述一种范式，通过单一的行为反应--声学惊吓反射--来衡量先前反复服用可卡因的长期缓解焦虑和引发焦虑的效果。根据体验的不同，愉悦和恐惧的状态都可以通过声音惊吓反应来衡量。惊吓在老鼠先前得到积极强化的环境中减少，反之，在恐惧条件作用后增加。这一范例将被用来检验这一假设，即皮质类固醇对戒断后反复服用可卡因的抗焦虑和致焦虑作用都是关键的。肾上腺切除的大鼠将被反复给予可卡因，然后在戒断一段时间后，将通过测量惊吓反射的幅度来测试快乐和恐惧的增加。皮质酮也将被用来试图逆转肾上腺切除术的影响。此外，还将评估药物对皮质酮产生的抑制作用。研究结果将表明，皮质类固醇是否对可卡因的愉悦和焦虑效应都是必需的，还是只对其中一种效应是必需的。这项研究将对理解环境和行为对可卡因的愉悦和焦虑特性的控制，以及应激激素是否同时调节这两种特性，或者是以不同的方式调节与可卡因相关的愉悦和焦虑具有重要意义。这些实验的结果应该对了解药物滥用和复发，以及制定治疗和预防策略产生影响。

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.