ENVIRONMENTAL INFLUENCES ON COCAINE SELF-ADMINISTRATION

尽管可卡因的长期非医疗使用目前已经达到 这个国家的疫情比例，到目前为止还没有明确的 卫生保健专业人员对最佳治疗的共识 应对可卡因滥用的策略。药理导论 提高可卡因戒断成功率的干预措施 直到最近才被调查，因为长期使用可卡因 历史上被认为会导致长期的生理戒断 停药后出现症状。然而，由于一些人可以留下来 休闲吸食毒品，除了可能有其他因素外 可卡因的强化特性决定了为什么其他人 强迫性药物使用的进展。事实上，慢性病的一个亚群 吸食可卡因的人可能实际上是在自我用药来调节痛苦的感觉 以及因吸毒而出现的精神症状。更好地理解 可能改变药物摄入量的潜在环境事件将会增加 了解药物成瘾的病因，并可能导致更多 有效和高效地治疗强迫性可卡因使用和戒断。 环境压力或焦虑的量或严重程度的变化可能是 使一些人倾向于服用强迫性药物的一个因素 使用，因为临床和临床前数据都涉及 苯二氮类药物在可卡因行为和神经生物学效应中的作用 在急性接触和长期停药期间。 因此，本提案中描述的实验将用于 系统调查可控和不可控的影响 电击应激对静脉输液的获取和维持作用 可卡因在大鼠体内的自我给药。此外，这种行为模式 将被用作评估各种药理作用是否 干预措施特别改变了药物摄取和/或行为影响 或者这些药物是否会导致非特异性 对动物的反应能力的影响。这些研究的结果 调查将增加对行为变量的了解，这些变量 可能有助于大鼠的可卡因自我给药，并可能 因此导致了新的药物疗法的发展 人类可卡因戒断和戒断的治疗。

Even though the chronic non-medical use of cocaine has currently reached epidemic proportions in this country, there is as yet no clear-cut consensus among health care professionals regarding optimal treatment strategies for cocaine abuse. The introduction of pharmacological interventions to increase the probability of successful cocaine abstinence has only recently been investigated 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. In fact, a subpopulation of chronic cocaine users may actually be self-medicating to regulate painful feelings and psychiatric symptoms via their 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. Changes in the amount or severity of environmental stress or anxiety may be one factor which predisposes some individuals to engage in compulsive drug use since both clinical and preclinical data have implicated an involvement of benzodiazepines in the behavioral and neurobiological effects of cocaine during both acute exposure and withdrawal from the chronic use of the drug. The experiments described in this proposal will therefore be used to systematically investigate the effects of controllable and uncontrollable electric footshock stress on the acquisition and maintenance of intravenous cocaine self-administration in rats. In addition, this behavioral model will be used as a baseline to evaluate whether various pharmacological interventions specifically alter drug-intake and/or the behavioral effects of withdrawal from cocaine or whether these drugs result in nonspecific effects on the ability of the animals to respond. The results of these investigations will increase knowledge of behavioral variables that potentially contribute to cocaine self-administration in rats and may therefore result in the development of novel pharmacotherapies in the treatment of cocaine withdrawal and abstinence in humans.