Circuit and epigenetic mechanisms underlying incubation of methamphetamine craving

甲基苯丙胺渴望潜藏的回路和表观遗传机制

基本信息

  • 批准号:
    9751825
  • 负责人:
  • 金额:
    $ 24.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-01 至 2021-07-31
  • 项目状态:
    已结题

项目摘要

Cue-induced drug craving progressively increases after withdrawal, a phenomenon termed ‘incubation of drug craving’. During the last decade, mechanistic studies have primarily focused on incubation of cocaine craving. In contrast, very few studies have examined the mechanisms underlying incubation of methamphetamine (Meth) craving. Here, I propose to study circuit and epigenetic mechanisms underlying incubation of Meth craving with a focus on the dorsal striatum (DS) region. The choice of this brain area is based on my preliminary data implicating a critical role of DS neuronal activity and a potential role of DS histone deacetylase 5 (HDAC5, an epigenetic-related enzyme) in incubation of Meth craving. At the circuit level, I will use a retrograde tracing technique (CTb, cholera toxin subunit B) in combination with the neuronal activity marker Fos to identify critical afferent projections to the DS that are activated during incubation of Meth craving. Next, I will use a novel retro-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) method to study the causal role of afferent projections to the DS in incubation of Meth craving. At the epigenetic level, I will combine chromatin immunoprecipitation-sequencing (ChIP-seq) with RNA-sequencing (RNA-seq) to identify downstream gene targets of HDAC5 in DS whose expression is altered after prolonged withdrawal (1 month) from Meth self-administration. I will also use the CRISPR-Cas9 system to examine the causal role of DS HDAC5 in incubation of Meth craving. My proposal will provide new insights on the mechanisms underlying Meth craving and relapse. Additionally, under the mentorship of Drs. Shaham, Nestler, and Cowan the proposal will provide me with an ideal training environment to prepare me for a future independent career as a researcher in an academic setting who explores basic mechanisms of drug addiction.
线索诱导的药物渴求在戒断后逐渐增加,这种现象被称为“潜伏期”

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 }}

Xuan Anna Li其他文献

Xuan Anna Li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('Xuan Anna Li', 18)}}的其他基金

March5 and Associated Mitochondrial Dynamics in Incubation of Oxycodone Craving
March5 和相关线粒体动力学在羟考酮渴望孵化中的作用
  • 批准号:
    10724668
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了