Conditioned place preference to amphetamine following prenatal immune activation

产前免疫激活后对安非他明的条件性位置偏好

基本信息

  • 批准号:
    8302069
  • 负责人:
  • 金额:
    $ 23.55万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-07-15 至 2014-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Addiction has been described as a disease of learning and memory, as the learning processes underlying acquisition, extinction, and reinstatement of drug-paired associations play a central role in human addictions. Our knowledge of specific environmental factors influencing drug-associated learning and memory is incomplete. A well-studied mechanism in other fields is prenatal infection, which stimulates maternal cytokines, soluble polypeptides mediating the innate inflammatory response. Consequences to the offspring of maternal cytokine elevation have been studied in an animal model termed "prenatal immune activation" using the synthetic nucleic acid poly I:C, which stimulates maternal cytokine expression. Injecting poly I:C during pregnancy alters function in the offspring of neuronal systems involved in response to drugs of abuse. Estimates from studies of other disorders suggest as many as 1/3 of drug dependent patients may have had in utero exposure to conditions stimulating maternal cytokine expression. The objective of this application is to characterize the effect of poly I:C injection on acquisition, extinction, and reinstatement of conditioned place preference to amphetamine. We will also identify neurochemical indices of relevance to these behaviors. Our overarching hypothesis is that prenatal immune activation alters glutamate and dopamine transmission in prefrontal cortex and nucleus accumbens, elements of the final common pathway mediating drug relapse, thereby impairing extinction and facilitating reinstatement of conditioned preference for drugs of abuse. We will test this hypothesis in Specific Aim 1 by determining the consequence of prenatal immune activation on acquisition, extinction, and drug- and stress-induced reinstatement of conditioned place preference to amphetamine. In Specific Aim 2, we will determine extracellular glutamate and dopamine in prefrontal cortex and nucleus accumbens preceding conditioning, and during drug-induced reinstatement following prenatal immune activation using microdialysis. Upon completion of these studies, we expect to demonstrate behavioral and neurochemical alterations following prenatal immune activation of direct relevance to the risk for drug relapse. Our expected findings may therefore suggest opportunities to detect a population at elevated risk for drug relapse, and simultaneously identify novel targets for intervention in this group. PUBLIC HEALTH RELEVANCE: We propose to determine the effect of prenatal immune activation on learning and memory associated with drug use. We also expect to identify neurochemical mechanisms contributing to the observed behavioral effects. Our expected outcomes are important because they will elucidate the effect of a common environmental exposure, prenatal immune activation, on a key outcome measure of relevance to drug dependence: learning and memory associated with drug use. The expected findings may advance the understanding of prevention, treatment, and prognosis for drug dependence.
描述(由申请人提供):成瘾被描述为一种学习和记忆疾病,因为药物配对关联的获得、消除和恢复的学习过程在人类成瘾中发挥着核心作用。我们对影响药物相关学习和记忆的特定环境因素的了解并不完整。其他领域经过充分研究的机制是产前感染,它会刺激母体细胞因子,即介导先天炎症反应的可溶性多肽。母体细胞因子升高对后代的影响已经在称为“产前免疫激活”的动物模型中进行了研究,该模型使用合成核酸聚 I:C,刺激母体细胞因子的表达。怀孕期间注射 Poly I:C 会改变后代对滥用药物做出反应的神经元系统的功能。对其他疾病的研究估计表明,多达 1/3 的药物依赖患者可能在子宫内曾接触过刺激母体细胞因子表达的条件。本申请的目的是表征聚 I:C 注射对安非他明条件性位置偏好的获得、消除和恢复的影响。我们还将确定与这些行为相关的神经化学指标。我们的总体假设是,产前免疫激活改变了前额皮质和伏核中谷氨酸和多巴胺的传递,这是介导药物复发的最终共同途径的要素,从而损害了灭绝并促进了对滥用药物的条件性偏好的恢复。我们将在具体目标 1 中通过确定产前免疫激活对安非他明条件性位置偏好的获得、消退以及药物和压力诱导的恢复的影响来检验这一假设。在具体目标 2 中,我们将使用微透析测定预处理前的前额皮质和伏核中的细胞外谷氨酸和多巴胺,以及产前免疫激活后药物诱导的恢复过程中的细胞外谷氨酸和多巴胺。完成这些研究后,我们希望证明产前免疫激活后的行为和神经化学变化与药物复发的风险直接相关。因此,我们预期的结果可能表明有机会检测药物复发风险较高的人群,并同时确定该人群的新干预目标。 公共卫生相关性:我们建议确定产前免疫激活对与吸毒相关的学习和记忆的影响。我们还期望确定有助于观察到的行为效应的神经化学机制。我们的预期结果很重要,因为它们将阐明常见环境暴露、产前免疫激活对与药物依赖相关的关键结果指标的影响:与药物使用相关的学习和记忆。预期的发现可能会增进对药物依赖的预防、治疗和预后的理解。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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

{{ 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 }}

NEIL MARK RICHTAND其他文献

NEIL MARK RICHTAND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('NEIL MARK RICHTAND', 18)}}的其他基金

Conditioned place preference to amphetamine following prenatal immune activation
产前免疫激活后对安非他明的条件性位置偏好
  • 批准号:
    8507697
  • 财政年份:
    2012
  • 资助金额:
    $ 23.55万
  • 项目类别:
Conditioned place preference to amphetamine following prenatal immune activation
产前免疫激活后对安非他明的条件性位置偏好
  • 批准号:
    8803091
  • 财政年份:
    2012
  • 资助金额:
    $ 23.55万
  • 项目类别:
Antipsychotics, hypoglycemia, glutamate and cognition
抗精神病药、低血糖、谷氨酸和认知
  • 批准号:
    7677249
  • 财政年份:
    2008
  • 资助金额:
    $ 23.55万
  • 项目类别:
Antipsychotics, hypoglycemia, glutamate and cognition
抗精神病药、低血糖、谷氨酸和认知
  • 批准号:
    7530688
  • 财政年份:
    2008
  • 资助金额:
    $ 23.55万
  • 项目类别:
Role of D3 dopamine receptor in behavioral sensitization
D3 多巴胺受体在行为敏化中的作用
  • 批准号:
    6862693
  • 财政年份:
    2004
  • 资助金额:
    $ 23.55万
  • 项目类别:
Role of D3 dopamine receptor in behavioral sensitization
D3 多巴胺受体在行为敏化中的作用
  • 批准号:
    7257089
  • 财政年份:
    2004
  • 资助金额:
    $ 23.55万
  • 项目类别:
Role of D3 dopamine receptor in behavioral sensitization
D3 多巴胺受体在行为敏化中的作用
  • 批准号:
    7024514
  • 财政年份:
    2004
  • 资助金额:
    $ 23.55万
  • 项目类别:
Role of D3 dopamine receptor in behavioral sensitization
D3 多巴胺受体在行为敏化中的作用
  • 批准号:
    6783258
  • 财政年份:
    2004
  • 资助金额:
    $ 23.55万
  • 项目类别:

相似海外基金

Relationship between neurotoxicity and the chemical structures of amphetamines
安非他明的神经毒性与化学结构的关系
  • 批准号:
    25860103
  • 财政年份:
    2013
  • 资助金额:
    $ 23.55万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Search for protein expression in amphetamines treated mouse heart : Challenge to the diagnosis for the sudden death of amphetamines abusers
寻找安非他明治疗小鼠心脏中的蛋白质表达:对安非他明滥用者猝死诊断的挑战
  • 批准号:
    22659138
  • 财政年份:
    2010
  • 资助金额:
    $ 23.55万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
  • 批准号:
    8312648
  • 财政年份:
    2010
  • 资助金额:
    $ 23.55万
  • 项目类别:
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
  • 批准号:
    8531900
  • 财政年份:
    2010
  • 资助金额:
    $ 23.55万
  • 项目类别:
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
  • 批准号:
    8715749
  • 财政年份:
    2010
  • 资助金额:
    $ 23.55万
  • 项目类别:
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
  • 批准号:
    8144930
  • 财政年份:
    2010
  • 资助金额:
    $ 23.55万
  • 项目类别:
Translational Genetics and Dopamine Signaling in Sensitivity to Amphetamines
安非他明敏感性中的转化遗传学和多巴胺信号传导
  • 批准号:
    7675601
  • 财政年份:
    2009
  • 资助金额:
    $ 23.55万
  • 项目类别:
Simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates and interaction in the rat
大鼠体内麻黄碱、安非他明、可卡因、可卡因代谢物和阿片类药物的同时测定及其相互作用
  • 批准号:
    17590585
  • 财政年份:
    2005
  • 资助金额:
    $ 23.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study for practical use of two chiral analyses of amphetamines by gas chromatography-mass spectrometry
气相色谱-质谱法对苯丙胺两种手性分析的实用化研究
  • 批准号:
    17590588
  • 财政年份:
    2005
  • 资助金额:
    $ 23.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Clinical Pharmacology of 3,4-Methylenedioxy Amphetamines
3,4-亚甲二氧基安非他明的临床药理学
  • 批准号:
    6870119
  • 财政年份:
    2004
  • 资助金额:
    $ 23.55万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了