Memory Destabilization and Cocaine-Cue Induced Reinstatement in Rat

大鼠记忆不稳定和可卡因诱导的恢复

基本信息

  • 批准号:
    10293792
  • 负责人:
  • 金额:
    $ 33.08万
  • 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 2026-04-30
  • 项目状态:
    未结题

项目摘要

Drug-associated conditioned stimuli (CS), or cues, contribute to both the progression and persistence of addiction. We hypothesize, as have others, that blocking reconsolidation of cocaine-cue memories could prevent cue-induced relapse. Reconsolidation is a process whereby reactivation of a memory renders it labile and vulnerable to disruption. Our published data, and that of others, confirm that limbic-striatal dopamine (DA)- dependent and several plasticity-regulated signaling mechanisms are involved in cocaine-cue reconsolidation processes. In this new proposal we hypothesize that violation of cocaine-cue expectancy renders a memory labile by triggering memory destabilization, thereby making cocaine-cue memories more sensitive to subsequent disruption by amnestic agents. The ability to induce the destabilization of cocaine-cue memories may be a key factor in enabling the use of targeted pharmacotherapies to block cocaine-cue memory reconsolidation and treat maladaptive memories. We propose to investigate directly the role of expectancy in reconsolidation of cocaine-cue memories and their impact on subsequent relapse-like behaviors by varying the difference between what is expected and experienced during reactivation and by photo stimulation of midbrain DA-containing VTA neurons to neutralize or induce prediction error (PE)-like signals. In Aim 1 we will reactivate cocaine memories by violating expectations of a) US (i.e., cocaine) magnitude and b) CS-US temporal contiguity. These manipulations should generate PE-like signals at the time of memory retrieval. According to our hypothesis and preliminary data, both positive and negative PE-like signals should induce destabilization and make the cue memory susceptible to blockade (i.e., reconsolidation) by an amnestic agent to reduce subsequent relapse to drug-seeking behavior. Relapse-like behaviors will include cue-induced and drug-primed reinstatement, and other measures, in male and female rats subjected to weeks of long-access cocaine self-administration. Select agents that potently and selectively alter memory reconsolidation processes – the protein-synthesis inhibitor anisomycin (ANI) and the histone acetyltransferase (HAT) inhibitor garcinol – will be used to render the destabilized memory subject to amnestic blockade. In Aim 2 we will optogenetic-based photostimulation of midbrain VTA DA neurons (TH-Cre+ rats) during cocaine-cue memory reactivation a) to artificially produce a dip or b) a spike in DA signaling, to artificially act as a negative or positive PE-like signal, respectively, to destabilize the cue memory and render it susceptible to amnestic blockade, ultimately reducing measures of cocaine relapse-like behaviors. Together these studies will define novel behavioral conditions whereby destabilization mechanisms can be used to make memories more susceptible to amnestic agents, to block reconsolidation of cocaine-cue memories, to reduce relapse-like behaviors, and to inspire the development of innovative therapeutic strategies for maladaptive memories.
药物相关条件刺激(CS),或提示,有助于进展和持续

项目成果

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Jane R Taylor其他文献

Sex chromosome complement regulates habit formation
性染色体组型调节习惯形成
  • DOI:
    10.1038/nn1994
  • 发表时间:
    2007-10-21
  • 期刊:
  • 影响因子:
    20.000
  • 作者:
    Jennifer J Quinn;Paul K Hitchcott;Elizabeth A Umeda;Arthur P Arnold;Jane R Taylor
  • 通讯作者:
    Jane R Taylor
Repeated, Intermittent Δ9-Tetrahydrocannabinol Administration to Rats Impairs Acquisition and Performance of a Test of Visuospatial Divided Attention
对大鼠重复、间歇性给予Δ9-四氢大麻酚会损害其对视觉空间分配注意测试的习得和表现
  • DOI:
    10.1038/sj.npp.1300316
  • 发表时间:
    2003-08-26
  • 期刊:
  • 影响因子:
    7.100
  • 作者:
    Christopher D Verrico;J David Jentsch;Robert H Roth;Jane R Taylor
  • 通讯作者:
    Jane R Taylor

Jane R Taylor的其他文献

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{{ truncateString('Jane R Taylor', 18)}}的其他基金

Memory Destabilization and Cocaine-Cue Induced Reinstatement in Rat
大鼠记忆不稳定和可卡因诱导的恢复
  • 批准号:
    10599998
  • 财政年份:
    2021
  • 资助金额:
    $ 33.08万
  • 项目类别:
Memory Destabilization and Cocaine-Cue Induced Reinstatement in Rat
大鼠记忆不稳定和可卡因诱导的恢复
  • 批准号:
    10441536
  • 财政年份:
    2021
  • 资助金额:
    $ 33.08万
  • 项目类别:
Decision-Making Dysfunction and Chronic Cocaine
决策功能障碍和慢性可卡因
  • 批准号:
    9236327
  • 财政年份:
    2017
  • 资助金额:
    $ 33.08万
  • 项目类别:
Individual Differences & Cocaine Effects on Impulsive Choice in Rat
个体差异
  • 批准号:
    10618290
  • 财政年份:
    2016
  • 资助金额:
    $ 33.08万
  • 项目类别:
Individual Differences & Cocaine Effects on Impulsive Choice in Rat
个体差异
  • 批准号:
    10361717
  • 财政年份:
    2016
  • 资助金额:
    $ 33.08万
  • 项目类别:
Individual differences & cocaine effects on impulsive choice in rats: D3/5HT1B
个体差异
  • 批准号:
    9282946
  • 财政年份:
    2016
  • 资助金额:
    $ 33.08万
  • 项目类别:
Individual differences & cocaine effects on impulsive choice in rats: D3/5HT1B
个体差异
  • 批准号:
    9891993
  • 财政年份:
    2016
  • 资助金额:
    $ 33.08万
  • 项目类别:
Cocaine, Impulsivity, and Stratal Function in Rats
可卡因、冲动和大鼠的层层功能
  • 批准号:
    7797707
  • 财政年份:
    2010
  • 资助金额:
    $ 33.08万
  • 项目类别:
Sex Differences in Alcohol Habit Formation in Rats: Corticostriatal Mechanisms
大鼠饮酒习惯形成的性别差异:皮质纹状体机制
  • 批准号:
    7528657
  • 财政年份:
    2008
  • 资助金额:
    $ 33.08万
  • 项目类别:
Sex Differences in Alcohol Habit Formation in Rats: Corticostriatal Mechanisms
大鼠饮酒习惯形成的性别差异:皮质纹状体机制
  • 批准号:
    7658974
  • 财政年份:
    2008
  • 资助金额:
    $ 33.08万
  • 项目类别:

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