Stress-Induced Marijuana Self-Administration: Role of Sex and Oxytocin

压力诱导的大麻自我管理：性和催产素的作用

基本信息

批准号：
8561004
负责人：
Suzette M Evans
金额：
$ 50.47万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8561004
关键词：
Address Applications Grants Attenuated Behavior Behavioral Behavioral Research Biological Factors Cannabinoids Cognition Cognitive Data Dependence Development Disease Drug abuse Drug usage Endocrine Exposure to Female Future Gender Role Goals Health High Prevalence Hormones Human Illicit Drugs Impulsivity Individual Interest Group Intervention Investigation Knowledge Laboratories Laboratory Animals Lead Link Literature Marijuana Marijuana Abuse Marijuana Dependence Marijuana Smoking Measures Mediating Modeling Oxytocin Physiological Placebos Plasma Play Process Public Health Relapse Research Risk Risk Behaviors Role Sampling Self Administration Sex Characteristics Sex Functioning Sexual Development Smoker Stress Stress Tests System Task Performances Techniques Testing Trier Social Stress Test Woman acute stress base biological adaptation to stress drug of abuse efficacy testing high risk hypothalamic-pituitary-adrenal axis improved male marijuana user men psychological stressor public health relevance response sex social stressor

项目摘要

DESCRIPTION (provided by applicant): Marijuana (MJ) use is prevalent, and has serious public health consequences, including a fast progression to dependence and a greater likelihood of engaging in other risky behaviors. This is of particular importance to women, who comprise a growing proportion of MJ smokers and are more likely to relapse than men. Treatment options for MJ smokers are currently limited and improved understanding of mechanisms that may trigger MJ use and the transition from MJ use to dependence is critical. The overarching goal of this grant proposal is to elucidate sex differences in processes mediating MJ use in non-treatment seeking, non-dependent regular users of MJ~ a group who is at great risk for developing MJ dependence. Therefore, in male and female MJ smokers, we will measure 1) the response to stress, a factor often implicated in drug abuse, using a standardized psychological stressor, and 2) stress-induced MJ self-administration. As a proof-of-concept approach we will administer intranasal (i.n.) oxytocin to test whether oxytocin, a hormone linked to the inhibition of stress response and potentially more effective in women, decreases stress and stress-induced MJ self-administration. Specifically, in MJ smokers, we will determine (1) sex differences in the behavioral and physiological stress response (Aim 1a) and subsequent MJ self-administration (Aim 1b) after exposure to a social stressor (Trier Social Stress Test~ TSST) compared to a stress-free (No Stress Test~ NST) condition through use of a naturalistic MJ self-administration paradigm~ and (2) the effects of i.n. oxytocin administratio compared with placebo on the behavioral response to TSST vs. NST (Aim 2a) and subsequent MJ self-administration (Aim 2b) in males compared to females (Aim 2c). Findings from this project will provide critical information for this particularly at-risk group of MJ smokers to bettr inform development of sex-specific interventions. Oxytocin administration, if effective in mitigating the behavioral response to stress, would strongly support our proposed mechanistic hypothesis and would support further exploration of possible intervention techniques for stress-induced MJ use. Results from this investigation will also lay critical groundwork for further research of behavioral and mechanistic factors underlying the continued use of MJ and the progression to dependence in MJ users, as well as users of other drugs of abuse.

描述（由申请人提供）：大麻 (MJ) 的使用很普遍，并且会产生严重的公共卫生后果，包括快速发展成依赖性以及更有可能从事其他危险行为。这对于女性来说尤其重要，因为她们在 MJ 吸烟者中所占的比例越来越大，并且比男性更容易复吸。 MJ 吸烟者的治疗选择目前有限，提高对可能引发 MJ 使用的机制的了解以及从 MJ 使用到依赖的转变至关重要。这项拨款提案的首要目标是阐明在不寻求治疗、不依赖 MJ 的经常使用者（这是一个极有可能发展 MJ 依赖的群体）中介导 MJ 使用过程中的性别差异。因此，在男性和女性 MJ 吸烟者中，我们将使用标准化的心理压力源来测量 1) 对压力的反应（通常与药物滥用有关的一个因素），以及 2) 压力引起的 MJ 自我给药。作为一种概念验证方法，我们将鼻内注射催产素来测试催产素（一种与抑制应激反应相关的激素，对女性可能更有效）是否可以减少压力和压力引起的 MJ 自我给药。具体来说，在 MJ 吸烟者中，我们将确定 (1) 行为和生理压力反应（目标 1a）的性别差异以及暴露于社会压力源（特里尔社会压力测试~ TSST）后随后的 MJ 自我管理（目标 1b）的性别差异通过使用自然主义的 MJ 自我管理范例，达到无压力（无压力测试 ~ NST）状态 ~ 和 (2) i.n. 的效果。与安慰剂相比，男性与女性（目标 2c）对 TSST 与 NST（目标 2a）以及随后 MJ 自我给药（目标 2b）的行为反应进行比较。该项目的研究结果将为 MJ 吸烟者这一高危群体提供重要信息，以便更好地为针对性别的干预措施的制定提供信息。催产素的施用，如果能有效减轻对压力的行为反应，将有力地支持我们提出的机制假设，并支持进一步探索压力诱导的 MJ 使用的可能干预技术。这项调查的结果还将为进一步研究 MJ 持续使用以及 MJ 使用者以及其他滥用药物使用者的依赖性进展的行为和机制因素奠定重要基础。