ENVIRONMENTAL INFLUENCES ON COCAINE SELF ADMINISTRATION

发现新的药理学干预措施，以增加 成功戒除可卡因的可能性一直很乏味， 长期使用可卡因在历史上并不被认为会产生 停药后生理性戒断症状延长。 然而，由于一些人可以保持休闲娱乐用户 除了可卡因的强化作用外， 决定为什么其他人会发展成强迫性的 吸毒更好地了解潜在的环境事件， 可以改变药物摄入量，增加对药物病因学的认识 成瘾，并可能导致更有效和更有效的治疗 可卡因的强迫性使用和戒断 金额的差异， 对环境压力或焦虑的严重性或敏感性可能是一种 使某些人易于吸毒的因素 使用.在为该项目供资的初期， 成功开发了行为范式， 暴露于无法控制的足震压力会增加 给老鼠注射可卡因 本文中描述的实验 应用程序旨在关注 药物干预，环境应激，应激激素 可卡因自我管理。急性和慢性治疗方案 与苯二氮卓类解痉剂（例如，利血平、阿普唑仑）， 非苯并二氮杂（例如，丁螺环酮、曲唑酮）以及 影响血浆皮质酮和ACTH（例如，甲吡酮）或与 肾上腺皮质类固醇受体（例如，醛固酮，螺内酯， 米非司酮）将在收购之前和之后进行调查 可卡因自我管理，以确定这些药物是否逆转 压力或压力激素的影响（例如，皮质酮，ACTH） 一旦这种行为开始和/或减弱药物摄入， 行为已经确立。此外，神经生物学 可能参与调解这些进程的机制 还将使用定量受体放射自显影术进行研究 和体内微透析。 这些调查的结果将 增加行为、神经生物学和神经内分泌知识 可能导致可卡因自我给药的变量 因此，可能有助于开发新的 治疗可卡因戒断的药物疗法， 人类的禁欲

The discovery of novel pharmacological interventions to increase the probability of successful cocaine abstinence has been tedious since chronic cocaine use has not historically been assumed to produce prolonged physiological withdrawal symptoms upon discontinuation. However, since some individuals can remain casual recreational users of the drug, there may be factors in addition to cocaine's reinforcing properties that determine why other individuals progress to compulsive drug use. A better understanding of potential environmental events that can alter drug intake will increase knowledge of the etiology of drug addiction and may result in the more effective and efficient treatment of compulsive cocaine use and withdrawal. Differences in the amount, severity or sensitivity to environmental stress or anxiety may be one factor which predisposes some individuals to engage in compulsive drug use. During the initial period of funding for this project, a behavioral paradigm was successfully developed which demonstrated that exposure to uncontrollable footshock stress increases vulnerability to self-administer cocaine in rats. The experiments described in this application were designed to focus on the interactions between pharmacological interventions, environmental stress, stress hormones and cocaine self-administration. Acute and chronic treatment regimens with benzodiazepine anxlolytics (e.g., chlordiazepoxide, alprazolam), non-benzodiazepines (e.g., buspirone, trazodone) as well as drugs which affect plasma corticosterone and ACTH (e.g., metyrapone) or bind to adrenocorticosteroid receptors (e.g., aldosterone, spironolactone, mifepristone) will be investigated before and following the acquisition of cocaine self-administration to determine if these drugs reverse the effects of stress or stress hormones (e.g.. corticosterone, ACTH) on the initiation of this behavior and/or attenuate drug-intake once this behavior has been established. In addition, the neurobiological mechanisms potentially involved in the mediation of these processes will also be investigated using quantitative receptor autoradiography and in vivo microdialysis. The results of these investigations will increase knowledge of behavioral, neurobiological and neuroendocrine variables that potentially contribute to cocaine self-administration in rats and may, therefore, assist in the development of novel pharmacotherapies for the treatment of cocaine withdrawal and abstinence in humans.