Sex, hormones and cocaine self-administration

性、激素和可卡因自我给药

基本信息

批准号：
6970115
负责人：
Wendy Jean Lynch
金额：
$ 7.63万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2007-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Despite the prevalence of cocaine addiction among women, few investigators have included females as subjects in cocaine self-administration experiments. Recent reports indicate gender differences in all phases of the addiction process including initiation and prevalence of use, patterns and levels of use, the progression to addiction, withdrawal, and relapse. While similar sex differences have also been observed in animals, few studies have investigated sex differences during the transition to addiction or the mechanisms that may underlie sex differences. Specific Aim 1 will characterize sex differences in cocaine self-administration behavior using a 24-hr access procedure that leads to high levels of intake and dysregulated patterns of use, features that may reflect compulsive aspects of addiction. An additional goal of Aim 1 is to explore the molecular and hormonal mechanisms that may underlie sex differences under high cocaine access conditions. Aim 2 will characterize the effects of high access to cocaine on subsequent motivational and behavioral changes and how these changes may differ by sex and ovarian hormone status. Specifically, we will investigate motivation to obtain cocaine as measured by responding under the progressive ratio schedule during early withdrawal (i.e., 0-72 hr) and after an extended drug-free period (i.e., 10-days). Additionally, since previous work has shown that chronic cocaine exposure produces not only motivational changes but is also associated with deficits in impulse control, Aim 3 will investigate the effects of high cocaine access on measures of impulsivity using a delay-discounting task. These experiments are of significance for drug abuse research and women's health research since they may help to identify molecular adaptations that occur following chronic cocaine self-administration and hormonal mechanisms that may underlie sex differences in vulnerability to cocaine addiction. Thus, these studies may provide a basis for the development of novel treatment strategies for cocaine abuse/dependence, particularly in women.

描述（由申请人提供）：尽管可卡因成瘾在女性中普遍存在，但很少有研究人员将女性作为可卡因自我给药实验的受试者。最近的报告表明，成瘾过程的所有阶段都存在性别差异，包括使用的开始和流行、使用的模式和水平、成瘾的进展、戒断和复发。虽然在动物中也观察到了类似的性别差异，但很少有研究调查成瘾过渡期间的性别差异或可能构成性别差异的机制。具体目标 1 将使用 24 小时获取程序来描述可卡因自我给药行为的性别差异，该程序会导致高水平的摄入和失调的使用模式，这些特征可能反映成瘾的强迫方面。目标 1 的另一个目标是探索在高可卡因获取条件下可能造成性别差异的分子和激素机制。目标 2 将描述大量获取可卡因对随后的动机和行为变化的影响，以及这些变化如何因性别和卵巢激素状态而异。具体来说，我们将调查获得可卡因的动机，通过在早期戒断期间（即 0-72 小时）和延长禁毒期（即 10 天）后根据渐进比例计划做出反应来衡量。此外，由于之前的研究表明，长期接触可卡因不仅会产生动机变化，而且还与冲动控制缺陷有关，因此目标 3 将使用延迟贴现任务来研究高可卡因获取对冲动测量的影响。这些实验对于药物滥用研究和妇女健康研究具有重要意义，因为它们可能有助于确定长期可卡因自我给药后发生的分子适应和可能导致可卡因成瘾脆弱性的性别差异的激素机制。因此，这些研究可能为开发针对可卡因滥用/依赖（尤其是女性）的新治疗策略提供基础。