NEUROENDOCRINE EFFECTS OF SELF ADMINISTERED COCAINE

描述：（申请人摘要） 可卡因在美国仍然是一种重要的滥用药物， 产生深远的行为影响，可卡因也扰乱了 神经内分泌功能。 药物作用的知识 滥用对神经内分泌功能的影响至关重要，因为它 提供了可能发生的病理生理变化的信息， 吸毒 可卡因刺激下丘脑-垂体-肾上腺（HPA）轴， HPA轴正常调节的中断可以影响 通过改变代谢维持生理稳态 葡萄糖蛋白质和脂肪 此外，免疫功能可能会受到损害， 以及对急性和慢性应激的反应和适应。 最近，很明显，暴露于压力源以及 HPA轴的药理学操作可以影响对 某些滥用药物的强化作用 因此，暴露于 应激源和随后HPA轴的激活可能在 在确定药物自我给药“脆弱性”方面的作用。 虽然 许多临床前研究检查可卡因对 神经内分泌功能的研究已经发表，但对神经内分泌功能的研究知之甚少。 可卡因自我给药对神经内分泌功能的影响。 所提出的实验的总体目标是利用实验性的 系统，可以对大鼠的血液进行采样以检测激素， 自我施用可卡因，以获得潜在的重要 HPA轴激活与药物之间关系的信息 自我管理。 拟议的研究将描述 自我服用可卡因与HPA激活之间的关系 轴上的剂量响应和时间过程数据， 可卡因的获得、维持、消退和重新开始阶段 自我管理。 假设主动（反应偶然） 与被动（非偶然反应）给予可卡因相比 差异影响HPA轴将通过比较受试者 在不同的应急反应下接受可卡因。 拟议 研究还将产生新的信息， HPA轴通过药理学和非药理学手段改变 自我服用可卡因对HPA轴的影响和增强 可卡因的特性。 这些实验的结果可以提供新的 以及对压力和药物寻求之间关系的重要见解 行为

DESCRIPTION: (Applicant's Abstract) Cocaine remains an important drug of abuse in the United States, and aside from producing profound behavioral effects, cocaine also disrupts neuroendocrine function in many species. Knowledge of the effects of drugs of abuse on neuroendocrine function is of fundamental importance because it provides information on the pathophysiological changes that can occur with drug use. Cocaine stimulates the hypothalamo-pituitary-adrenal (HPA) axis, and disruption of the normal regulation of the HPA axis can affect the maintenance of physiologic homeostasis by altering the metabolism of glucose, proteins and fats. In addition, immune function can be compromised as well as the reaction and adaptation to acute and chronic stress. Recently it has become apparent that exposure to stressors as well as pharmacological manipulation of the HPA axis can affect the responses to and the reinforcing properties of some drugs of abuse. Thus, exposure to stressors and subsequent activation of the HPA axis might play a critical role in determining "vulnerability" to drug self-administration. Although numerous preclinical studies examining the effects of cocaine on neuroendocrine function have been published, little is known about the effects of the self-administration of cocaine on neuroendocrine function. The overall goal of the proposed experiments is to utilize an experimental system where blood can be sampled for hormones in rats during the self-administration of cocaine in order to obtain potentially important information on the relationships between activation of the HPA axis and drug self-administration. The proposed studies will characterize the relationships between self-administered cocaine and activation of the HPA axis by generating dose response and time course data during the acquisition, maintenance, extinction and re-initiation phases of cocaine self-administration. The hypothesis that the active (response contingent) versus passive (response non-contingent) administration of cocaine differentially affects the HPA axis will be tested by comparing subjects that receive cocaine under different response contingencies. The proposed studies also will generate new information on whether prior activation of the HPA axis through pharmacologic and non-pharmacologic means alters the effects of self-administered cocaine on the HPA axis and the reinforcing properties of cocaine. The results of these experiments could provide new and important insights on the relationships between stress and drug seeking behavior.