ENVIRONMENTAL INFLUENCES ON COCAINE SELF ADMINISTRATION

本修订后的竞争性延续申请建议继续进行 研究环境压力的影响以及随后的 激活HPA轴的启动和维持 大鼠静脉内可卡因自我给药。 主要假设 这些实验的基础是， 可卡因的作用至少部分是通过 常见的神经生物效应系统也会被压力激活。 迄今收集的数据表明， 可卡因强化中的皮质酮，初步数据表明， 这种激素在糖皮质激素或II型 肾上腺皮质类固醇受体负责这种作用。 第一个实验将研究 肾上腺皮质激素在交替的，多个 食物强化和可卡因自我给药时间表， 确定肾上腺皮质激素对静脉注射可卡因的影响 自我给药是对可卡因采取特定行动的结果 增强或非特异性影响大鼠的能力， 回答。后续实验还将研究 肾上腺皮质激素在静脉注射可卡因自我获得中的作用 大鼠给药。 最后，实验提出，将 确定肾上腺皮质类固醇是否也参与了 在暴露于压力的大鼠中观察到对可卡因的敏感性增加。 另一系列的实验将研究 肾上腺皮质激素在静脉注射可卡因自我恢复中的作用 给药，以确定肾上腺皮质类固醇在此 渴望的动物模型 能有效阻断 电击脚和/或可卡因引起的 寻求可卡因的行为也可能有效地缓解症状 对可卡因的渴望 其他实验将研究 应激和肾上腺皮质激素在辨别性认知障碍中的作用 可卡因的刺激作用，以确定是否主观 可卡因的强化作用是通过类似的 机制等 这些实验将增加关于压力和 HPA轴的随后激活影响可卡因 加强，也可能提出新的药物治疗， 人类可卡因滥用和戒断的治疗。

This revised competing continuation application proposes to proceed with investigations of the effects of environmental-stress and the subsequent activation of the HPA axis on the initiation and maintenance of intravenous cocaine self-administration in rats. The primary hypothesis underlying these experiments is that the reinforcing and subjective effects of cocaine are mediated, at least in part, through interactions with common neurobiological effector systems also activated by stress. Data collected to date have demonstrated an important role for corticosterone in cocaine reinforcement, and preliminary data suggest that it is the actions of this hormone at glucocorticoid or Type II adrenocorticosteroid receptors that are responsible for this effect. The first experiments will investigate the effects of adrenocorticosteroids on responding under an alternating, multiple schedule of food reinforcement and cocaine self-administration to determine if the effects of adrenocorticosteroids on intravenous cocaine self-administration are the result of specific actions on cocaine reinforcement or nonspecific effects on the ability of the rats to respond. Follow-up experiments will also investigate the role for adrenocorticosteroids in the acquisition of intravenous cocaine self- administration in rats. Finally, experiments are proposed that will determine whether or not adreno-corticosteroids are also involved in the increased sensitivity to cocaine observed in rats exposed to stress. Another series of experiments will investigate the effects of adrenocorticosteroids in the reinstatement of intravenous cocaine self- administration to determine the effects of adrenocorticosteroids in this animal model of craving. Drugs which are effective in blocking the electric footshock and/or cocaine-induced reinstatement of cocaine-seeking behavior may also be effective in alleviating symptoms of cocaine craving in humans. Other experiments will investigate the effects of stress and adrenocorticosteroids in the discriminative stimulus effects of cocaine to determine whether or not the subjective and reinforcing effects of cocaine are mediated through similar mechanisms. These experiments will increase knowledge of how stress and the subsequent activation of the HPA axis influence cocaine reinforcement and may also suggest novel pharmacotherapies for the treatment of cocaine abuse and withdrawal in humans.