Effects of Chronic Cannabis Use on the Neuroendocrine Stress Response

长期吸食大麻对神经内分泌应激反应的影响

基本信息

  • 批准号:
    10439578
  • 负责人:
  • 金额:
    $ 7.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY The most commonly cited reason for habitual cannabis use is to cope with stress. Although this may provide acute beneficial effects, the long-term ramifications of chronic cannabis use, particularly under drug-free conditions, remain unknown. We have demonstrated that sober chronic cannabis users display blunted psychological and physiological responses to an acute laboratory stressor relative to non-users. However, this cross-sectional approach precludes the ability to establish causal relationships between cannabis use and the stress response. Preclinical animal models are particularly advantageous in this respect, yet current models of cannabis use have been plagued by methodological concerns that limit the translatability of these data to human populations. To address these limitations, our laboratory has generated important new data using a novel, translationally relevant model of cannabis vapor self-administration that uses response-contingent delivery of vaporized cannabis extracts containing high concentrations of Δ9 tetrahydrocannabinol. This approach is unique in that it uses volitional exposure to natural cannabis extracts (rather than forced delivery of synthetic cannabinoid receptor agonists or isolated cannabis constituents) that are delivered via the pulmonary route of administration that is most common in human users. We will use this approach in the current proposal to determine whether cannabis vapor self-administration causes alterations in basal and stress-induced activation of the hypothalamic- pituitary-adrenal (HPA) stress axis in male and female rats. In Aim 1, we will use immunohistochemistry to quantify activation of the immediate early gene c-fos in different cell types within the paraventricular nucleus (PVN) of the hypothalamus of male and female rats trained to self-administer varying concentrations of cannabis or vehicle vapor. In Aim 2, we will perform radioimmunoassays on plasma harvested from cannabis-exposed and non-exposed rats in stress and no-stress conditions to determine the extent to which chronic volitional cannabis exposure alters basal and stress-induced recruitment of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Additionally, brains will be extracted to assess corticotropin-releasing hormone (CRH) peptide content in the central nucleus of the amygdala of cannabis-exposed and non-exposed rats under stress or non-stress conditions. We predict that rats trained to self-administer cannabis vapor will exhibit dose- dependent elevations in basal CORT, attenuated stress-induced activation of CRH-positive PVN neurons, increased reliance on passive coping strategies, and dampened recruitment of ACTH, CORT and CRH content relative to vehicle-exposed rats. Results from these studies will provide a foundation for understanding long-term consequences of chronic cannabis use and allow us to identify causal relationships between cannabis use and stress reactivity. Moreover, this work will support the feasibility of future studies that will investigate the mechanisms underlying these effects and identify whether alterations in the stress response are a risk factor for developing problematic cannabis use.
项目总结 习惯性吸食大麻最常被引用的理由是为了应对压力。尽管这可能会提供 急性有益影响,长期使用大麻的长期后果,特别是在无毒品的情况下 情况,仍不得而知。我们已经证明,戒酒的慢性大麻使用者表现迟钝 相对于非使用者而言,对急性实验室应激源的心理和生理反应。不过,这个 横断法排除了确定大麻使用与 压力反应。临床前动物模型在这方面特别有利,但目前的动物模型 大麻的使用一直受到方法论问题的困扰,限制了这些数据对人类的可译性 人口。为了解决这些限制,我们的实验室使用一种新的、 使用响应应急递送的大麻蒸气自我给药的翻译相关模型 含有高浓度Δ-9四氢大麻酚的大麻挥发提取物。这种方法是独一无二的 这是因为它使用自愿接触天然大麻提取物(而不是强制交付合成大麻素 受体激动剂或分离的大麻成分)通过肺部给药途径给药 这在人类用户中最为常见。我们将在目前的提案中使用这种方法来确定是否 大麻蒸气自身给药导致基础和应激诱导的下丘脑激活改变- 雄性和雌性大鼠垂体-肾上腺(HPA)应激轴。在目标1中,我们将使用免疫组织化学来 即刻早期基因c-fos在室旁核不同细胞类型中的激活 不同浓度大麻对雄性和雌性大鼠下丘脑下丘脑(PVN)的影响 或者是汽车尾气。在目标2中,我们将对接触大麻的血浆进行放射免疫分析。 和非暴露大鼠在应激和非应激条件下确定慢性意志的程度 大麻暴露改变基础和应激诱导的促肾上腺皮质激素(ACTH)和 皮质酮(CORT)。此外,还将提取大脑以评估促肾上腺皮质激素释放激素(CRH)。 应激大鼠与非大麻大鼠杏仁中央核多肽含量的比较 或无压力的情况下。我们预测,接受过自我管理大麻蒸气训练的大鼠将表现出剂量- 基础皮质区的依赖性升高,减弱应激诱导的CRH阳性PVN神经元的激活, 更多地依赖被动应对策略,抑制了ACTH、CORT和CRH含量的招募 相对于接触车辆的大鼠。这些研究的结果将为理解长期的 长期使用大麻的后果,并使我们能够确定大麻使用和使用之间的因果关系 应激反应。此外,这项工作将支持未来研究的可行性,这些研究将调查 这些效应的潜在机制,并确定应激反应的变化是否为 开发有问题的大麻使用。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A review of the effects of acute and chronic cannabinoid exposure on the stress response.
  • DOI:
    10.1016/j.yfrne.2021.100945
  • 发表时间:
    2021-10
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Glodosky NC;Cuttler C;McLaughlin RJ
  • 通讯作者:
    McLaughlin RJ
Cannabis vapor self-administration elicits sex- and dose-specific alterations in stress reactivity in rats.
大麻蒸气自我给药会引起大鼠应激反应性的性别和剂量特异性改变。
  • DOI:
    10.1016/j.ynstr.2020.100260
  • 发表时间:
    2020-11
  • 期刊:
  • 影响因子:
    5
  • 作者:
    Glodosky NC;Cuttler C;Freels TG;Wright HR;Rojas MJ;Baglot SL;Hill MN;McLaughlin RJ
  • 通讯作者:
    McLaughlin RJ
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Ryan Joseph McLaughlin其他文献

Ryan Joseph McLaughlin的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Ryan Joseph McLaughlin', 18)}}的其他基金

Establishing Behavioral and Biological Predictors of Problematic Cannabis Use
建立有问题的大麻使用的行为和生物预测因子
  • 批准号:
    10388270
  • 财政年份:
    2021
  • 资助金额:
    $ 7.65万
  • 项目类别:
Endocannabinoid Modulation of the Habenular Stress Response
内源性大麻素对缰核应激反应的调节
  • 批准号:
    10305687
  • 财政年份:
    2020
  • 资助金额:
    $ 7.65万
  • 项目类别:
Endocannabinoid Modulation of the Habenular Stress Response
内源性大麻素对缰核应激反应的调节
  • 批准号:
    10516731
  • 财政年份:
    2020
  • 资助金额:
    $ 7.65万
  • 项目类别:
Effects of developmental cannabis exposure on prefrontocortical structure and function
发育期大麻暴露对前额皮质结构和功能的影响
  • 批准号:
    9453312
  • 财政年份:
    2017
  • 资助金额:
    $ 7.65万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.65万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了