A Novel Emotional Stress Model of Co-morbid Opiate Use and Mood Disorders
阿片类药物使用和情绪障碍共病的新型情绪压力模型
基本信息
- 批准号:8824128
- 负责人:
- 金额:$ 11.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-02-01 至 2016-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdolescentAdultAffectBehaviorBehavioralBehavioral ResearchChronicChronic stressComorbidityConsumptionCoupledDataDependenceDevelopmentDiseaseDopamineDrug AddictionDrug abuseEmotionalEmotional StressExposure toFaceFutureGoalsHealthIntakeLeadMediatingMental DepressionMental disordersMindMissionModelingMolecularMood DisordersMorphineMusNIH Program AnnouncementsNational Institute of Drug AbuseOpiate AddictionOpiatesOralPainPharmaceutical PreparationsPopulationPost-Traumatic Stress DisordersPre-Clinical ModelPredispositionProcessProtocols documentationPsychological StressPublic HealthResearchResearch PersonnelRewardsRodent ModelRoleSignal TransductionSocial DevelopmentSocial InteractionSpecific qualifier valueStressTechniquesTraumaTreatment EfficacyVentral Tegmental AreaViralWorkacute stressaddictiondepressive symptomsdopaminergic neurondrinkingeffective interventionexperienceinterestmouse modelneurobiological mechanismnew therapeutic targetnovelnovel therapeuticsopioid abusepost-traumatic stresspreferenceprogramspublic health relevanceresponsesocialtool
项目摘要
DESCRIPTION (provided by applicant): Co-morbidity of opiate use and mood disorders such as depression and post-traumatic stress is a significant health and financial burden, one that will
likely increase given the increase in both abuse and prescription of pain-relieving opiate drugs in
the US. Most preclinical models of mood disorders, such as chronic social defeat stress, involve a physical trauma, thus complicating the study of pain-relieving opiate drugs. It is critical to develop a preclinical model that lacks the confound of physical pain to evaluate the molecular mechanisms that underlie opiate abuse and the impact of stress on initiating or exacerbating use. This proposal aims to use the recently developed emotional stress model to address the central hypothesis that exposure to chronic psychological stress impacts morphine reward and consumption and can serve as a mouse model of co-morbid opiate dependence and mood disorders. The chronic social defeat stress model has strong face validity for post- traumatic stress disorder and depression and a dependence on altered ventral tegmental area dopamine neuron activity. A modified version of this protocol lacking physical pain called chronic emotional
stress, in which mice witness but are not physically exposed to social defeat stress, will be used to evaluate the effect of emotional stress on morphine reward and consumption. Specific Aim 1 will determine whether exposure to physical or emotional social defeat stress alters morphine reward using conditioned place preference. Specific Aim 2 will evaluate whether chronic physical or emotional stress alters the voluntary intake of morphine using a two-bottle preference paradigm that takes advantage of the C57BL/6J strain's propensity to consuming oral morphine. Specific Aim 3 will determine whether mice exposed to chronic emotional stress alter their drinking during the stress experience, and what effect consumption of morphine during stress has on the expression of stress-induced behavioral changes such as social avoidance. Preliminary data are presented that show susceptibility to physical social defeat stress increases morphine reward and that there is a negative correlation between social interaction score and morphine preference, indicative of depressive-like behavior increasing morphine reward. It is expected that emotional stress will produce a similar effect, with mice susceptible to emotional stress showing an increase in preference for morphine. Data are also presented that following chronic physical and emotional stress voluntary morphine consumption is increased and that consumption is negatively correlated with social interaction. It is expected that mice will also increase morphine consumption during emotional stress, exacerbating stress-induced behavioral changes such as social avoidance. Completion of the proposed work will provide a novel model of co-morbid mood disorders and opiate use that can be utilized in future studies to examine the molecular mechanisms that underlie behavioral changes induced by opiate drugs or stress, a necessary step in the development of novel therapeutic options.
描述(由申请人提供):阿片类药物使用与情绪障碍(如抑郁症和创伤后应激障碍)的共病是一项重大的健康和经济负担,
鉴于阿片类止痛药物的滥用和处方增加,这一数字可能会增加
美国。大多数情绪障碍的临床前模型,例如慢性社交失败压力,都涉及身体创伤,从而使止痛阿片类药物的研究变得复杂化。开发一种不受身体疼痛影响的临床前模型来评估阿片类药物滥用的分子机制以及压力对开始或加剧使用的影响至关重要。该提案旨在利用最近开发的情绪压力模型来解决核心假设,即暴露于慢性心理压力会影响吗啡奖励和消耗,并可以作为共病阿片依赖和情绪障碍的小鼠模型。慢性社会失败压力模型对于创伤后应激障碍和抑郁症具有很强的表面效度,并且依赖于改变的腹侧被盖区多巴胺神经元活动。该方案的修改版本缺乏身体疼痛,称为慢性情绪
压力,即小鼠目睹但没有身体暴露于社交失败压力,将用于评估情绪压力对吗啡奖励和消费的影响。具体目标 1 将使用条件性位置偏好来确定暴露于身体或情感社交失败压力是否会改变吗啡奖励。具体目标 2 将使用两瓶偏好范式评估慢性身体或情绪压力是否会改变吗啡的自愿摄入,该范式利用了 C57BL/6J 菌株消耗口服吗啡的倾向。具体目标 3 将确定暴露于慢性情绪压力的小鼠在压力经历期间是否会改变其饮酒行为,以及压力期间吗啡的消耗对压力引起的行为变化(例如社交回避)的表达有何影响。初步数据显示,对身体社交失败压力的敏感性会增加吗啡奖励,并且社交互动得分与吗啡偏好之间存在负相关,表明抑郁样行为会增加吗啡奖励。预计情绪压力也会产生类似的效果,易受情绪压力影响的小鼠对吗啡的偏好会增加。数据还显示,长期身体和情绪压力后,吗啡的自愿消耗量会增加,并且消耗量与社交互动呈负相关。预计小鼠在情绪压力期间也会增加吗啡消耗量,从而加剧压力引起的行为变化,例如社交回避。完成拟议的工作将提供一种共病情绪障碍和阿片类药物使用的新模型,可用于未来的研究,以检查阿片类药物或压力引起的行为变化的分子机制,这是开发新型治疗方案的必要步骤。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.
- DOI:10.1016/j.neuropharm.2017.02.001
- 发表时间:2017-05-01
- 期刊:
- 影响因子:4.7
- 作者:Kaska S;Brunk R;Bali V;Kechner M;Mazei-Robison MS
- 通讯作者:Mazei-Robison MS
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Michelle Suzanne Mazei-Robison其他文献
Michelle Suzanne Mazei-Robison的其他文献
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{{ truncateString('Michelle Suzanne Mazei-Robison', 18)}}的其他基金
Role for novel ventral tegmental area neuromedin S neurons in morphine responses
新型腹侧被盖区神经调节素 S 神经元在吗啡反应中的作用
- 批准号:
10739543 - 财政年份:2023
- 资助金额:
$ 11.51万 - 项目类别:
Projection-specific gene expression in resilience to chronic stress
慢性应激恢复能力中的投射特异性基因表达
- 批准号:
10683942 - 财政年份:2016
- 资助金额:
$ 11.51万 - 项目类别:
Neurobiological Mechanisms Underlying Stress-Induced Changes in Opiate Reward
压力引起的阿片奖励变化的神经生物学机制
- 批准号:
9352306 - 财政年份:2016
- 资助金额:
$ 11.51万 - 项目类别:
Projection-specific gene expression in resilience to chronic stress
慢性应激恢复能力中的投射特异性基因表达
- 批准号:
10444242 - 财政年份:2016
- 资助金额:
$ 11.51万 - 项目类别:
Characterization of the Role of mTOR Signaling in Opiate Action
mTOR 信号传导在阿片类药物作用中的作用表征
- 批准号:
7545148 - 财政年份:2008
- 资助金额:
$ 11.51万 - 项目类别:
Characterization of the Role of mTOR Signaling in Opiate Action
mTOR 信号传导在阿片类药物作用中的作用表征
- 批准号:
7922609 - 财政年份:2008
- 资助金额:
$ 11.51万 - 项目类别:
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