TAAR 1 modulation of addiction-related effects of nicotine

TAAR 1 调节尼古丁成瘾相关效应

基本信息

  • 批准号:
    9307798
  • 负责人:
  • 金额:
    $ 21.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-07-01 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

ABSTRACT Tobacco smoking remains a major public health concern globally. Although there are FDA-approved therapeutic options available, they are far from adequate to maintain long-term smoking abstinence in most smokers. Thus, discovering novel efficacious pharmacotherapies to aid in smoking cessation remains an urgent clinical need. Nicotine, the major component in tobacco that is responsible for tobacco addiction, stimulates the mesolimbic dopaminergic system via activating nicotinic acetylcholine receptors (nAChRs). Nicotine replacement therapy and the nAChR partial agonist varenicline have achieved limited clinical success by directly modulating the central nAChRs. Indirect modulation of dopaminergic system by non-dopaminergic mechanism may also be able to modulate the addiction-related effects of nicotine. Trace amine associated receptor 1 (TAAR 1) has emerged as a novel target for the development of potential pharmacotherapy to treat drug addiction. In particular, the neuronal distribution of TAAR 1 overlaps with many key regions of the reward pathway, and biochemical studies reveal robust interactions between TAAR 1 signaling and dopamine transporters and D2 receptors. TAAR 1 agonists have been shown to attenuate several addiction-related behavioral effects of cocaine and methamphetamine. However, it is unknown of the role of TAAR 1 in mediating nicotine addiction. We recently observed that a selective TAAR 1 partial agonist, RO5263397, markedly attenuates nicotine induced behavioral sensitization and the discriminative stimulus effects of nicotine. The objective of the present application is to examine the hypothesis that TAAR 1 is a novel drug target for the treatment of nicotine addiction. This hypothesis will be tested by pursuing two specific aims: 1) examine the effects of TAAR 1 full agonist RO5166017 and partial agonist RO5263397 on nicotine self- administration using both fixed ratio and progressive ratio schedules of reinforcement (Aim 1); 2) examine the effects of RO5166017 and RO5263397 on nicotine-associated cue- and nicotine prime-induced reinstatement of extinguished nicotine-seeking behavior (Aim 2). Collectively, the proposed studies systematically evaluate the effects of TAAR 1 agonists on the addiction-related (e.g., reinforcing and reinstatement) effects of nicotine. These data will provide valuable information on the role of TAAR 1 in mediating nicotine addiction. In addition, data obtained in the proposed investigation may contribute to the identification of novel TAAR 1-based pharmacotherapy for smoking cessation.
摘要

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Interleukin-1 receptor-associated kinase 4 (IRAK4) in the nucleus accumbens regulates opioid-seeking behavior in male rats.
  • DOI:
    10.1016/j.bbi.2021.12.014
  • 发表时间:
    2022-03
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wu R;Liu J;Vu J;Huang Y;Dietz DM;Li JX
  • 通讯作者:
    Li JX
TAAR1 in Addiction: Looking Beyond the Tip of the Iceberg.
  • DOI:
    10.3389/fphar.2018.00279
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Liu JF;Li JX
  • 通讯作者:
    Li JX
Activation of trace amine-associated receptor 1 attenuates nicotine withdrawal-related effects.
  • DOI:
    10.1111/adb.13075
  • 发表时间:
    2022-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Wu R;Liu J;Johnson B;Huang Y;Zhang Y;Li JX
  • 通讯作者:
    Li JX
Modulating reconsolidation and extinction to regulate drug reward memory.
TAAR1 and Psychostimulant Addiction.
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Jun-Xu Li其他文献

Jun-Xu Li的其他文献

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{{ truncateString('Jun-Xu Li', 18)}}的其他基金

Development of LPA5 Antagonists as Analgesics
LPA5 拮抗剂镇痛药的开发
  • 批准号:
    10638278
  • 财政年份:
    2023
  • 资助金额:
    $ 21.22万
  • 项目类别:
TAAR1 agonists for nicotine addiction
TAAR1 激动剂治疗尼古丁成瘾
  • 批准号:
    10561715
  • 财政年份:
    2019
  • 资助金额:
    $ 21.22万
  • 项目类别:
TAAR1 agonists for nicotine addiction
TAAR1 激动剂治疗尼古丁成瘾
  • 批准号:
    9892992
  • 财政年份:
    2019
  • 资助金额:
    $ 21.22万
  • 项目类别:
TAAR1 agonists for nicotine addiction
TAAR1 激动剂治疗尼古丁成瘾
  • 批准号:
    10353373
  • 财政年份:
    2019
  • 资助金额:
    $ 21.22万
  • 项目类别:
TAAR1 agonists for nicotine addiction
TAAR1 激动剂治疗尼古丁成瘾
  • 批准号:
    10092996
  • 财政年份:
    2019
  • 资助金额:
    $ 21.22万
  • 项目类别:
TAAR 1 modulation of addiction-related effects of nicotine
TAAR 1 调节尼古丁成瘾相关效应
  • 批准号:
    9182100
  • 财政年份:
    2016
  • 资助金额:
    $ 21.22万
  • 项目类别:
Imidazoline I2 receptors as targets for the treatment of pain
咪唑啉 I2 受体作为治疗疼痛的靶点
  • 批准号:
    9186516
  • 财政年份:
    2013
  • 资助金额:
    $ 21.22万
  • 项目类别:
IMIDAZOLINE I2 RECEPTORS AS TARGETS FOR THE TREATMENT OF PAIN
咪唑啉 I2 受体作为治疗疼痛的靶点
  • 批准号:
    9170057
  • 财政年份:
    2013
  • 资助金额:
    $ 21.22万
  • 项目类别:
Imidazoline I2 receptors as targets for the treatment of pain
咪唑啉 I2 受体作为治疗疼痛的靶标
  • 批准号:
    8970695
  • 财政年份:
    2013
  • 资助金额:
    $ 21.22万
  • 项目类别:
Behavioral effects of methamphetamine & imidazoline I2 receptor ligands
甲基苯丙胺对行为的影响
  • 批准号:
    8581533
  • 财政年份:
    2013
  • 资助金额:
    $ 21.22万
  • 项目类别:

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Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation
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A novel nanobody-based agonist-redirected checkpoint (ARC) molecule, aPD1-Fc-OX40L, for cancer immunotherapy
一种基于纳米抗体的新型激动剂重定向检查点 (ARC) 分子 aPD1-Fc-OX40L,用于癌症免疫治疗
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    2023
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  • 项目类别:
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