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：
8992903
负责人：
Suzette M Evans
金额：
$ 48.35万
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 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8992903
关键词：
Address Applications Grants Attenuated Behavior Behavioral Behavioral Mechanisms Behavioral Research Biological Factors Cannabinoids Cognition Data Dependence Development 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 behavioral response biological adaptation to stress cognitive task drug of abuse efficacy testing high risk hypothalamic-pituitary-adrenal axis illicit drug use improved male marijuana use marijuana use disorder marijuana user men psychological stressor 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，并且具有严重的公共卫生后果，包括对依赖性的快速发展和更大的可能性参与其他风险行为。这对女性尤其重要，这些妇女构成了越来越多的MJ吸烟者，并且比男性更有可能复发。目前，MJ吸烟者的治疗选择是有限的，并且对可能触发MJ使用的机制的理解有所改善，并且从MJ使用到依赖的过渡至关重要。该赠款提案的总体目标是阐明介导MJ在非治疗寻求，非依赖的常规用户中使用MJ〜的过程中的性别差异，该小组有很大的风险发展MJ依赖。因此，在男性和女性MJ吸烟者中，我们将测量1）对压力的反应，这是使用标准的心理压力源与药物滥用有关的因素，以及2）压力引起的MJ自我给药。作为一种概念验证方法，我们将施用鼻内（I.N.）催产素来测试催产素是否与抑制压力反应的激素相关，并可能在女性中更有效，可降低压力和压力诱导的MJ自我治疗。具体而言，在MJ吸烟者中，我们将确定（1）在暴露于社会压力源（TRIER社会压力测试〜TSST）后，行为和生理压力反应（AIM 1A）以及随后的MJ自我给药（AIM 1B）的性别差异（AIM 1B）与无压力（无压力测试）（无压力测试〜NST）通过使用自然的MJ自我效应。与女性相比，与安慰剂相比，与安慰剂相比，与安慰剂相比，男性对TSST与NST（AIM 2A）的行为反应（AIM 2A）（AIM 2B）与女性相比（AIM 2C）（AIM 2C）。该项目的发现将为这一特别危险的MJ吸烟者提供关键信息，以告知性别特定干预措施的发展。催产素给药，如果有效缓解对压力的行为反应，将强烈支持我们提出的机械假设，并将支持进一步探索可能用于压力引起的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的行为和机械因素进一步研究，并继续使用MJ以及对MJ使用者的依赖以及其他滥用药物的使用者的依赖。