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Role of hypothalamic-specific POMC deficiency in alcohol reward and drinking

Role of hypothalamic-specific POMC deficiency in alcohol reward and drinking
下丘脑特异性 POMC 缺乏在酒精奖励和饮酒中的作用
批准号:
9137600
负责人:
YAN ZHOU
金额:
$8.48万
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
项目状态:
已结题
起止时间:
2015-09-05 至 2018-08-31

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英文摘要
 DESCRIPTION (provided by applicant): Opioidergic mechanisms particularly through beta-endorphin are involved in reward and drug addiction. In different rodent models of alcohol intake, opioid receptor antagonists decrease alcohol consumption and relapse-like drinking. Beta-endorphin is encoded by pro-opiomelanocortin (POMC) gene. Using Sardinian alcohol-preferring rats and C57BL/6J, we recently found that voluntary alcohol drinking for 2 weeks increases POMC gene expression in the hypothalamus of both rats and mice. Our hypothesis is that alterations of hypothalamic POMC gene expression are critical to alcohol-induced reward and the development of alcohol drinking behaviors, dependence and relapse. In transgenic mice, deletion of POMC nPEs (hypothalamic- specific POMC enhancers) abolishes POMC expression selectively in the hypothalamus, but with normal pituitary POMC cells. Our first goal (Specific Aim 1) is to determine the roles of hypothalamic POMC neurons in regulating alcohol reward and drinking behaviors in male and female nPE knockout mice, using drinking-in-the- dark (DID), chronic escalation drinking (CED) and conditioned place preference (CPP) models. The hypothesized reduction by POMC nPE deletion of alcohol behaviors would provide the experimental evidence that hypothalamic POMC neurons are involved in alcohol rewarding or relapse-like drinking, and the conserved POMC nPE enhancers between mice and men could provide a valuable platform for the discovery of transcription factors controlling the POMC expression, and then alcohol drinking. New therapeutic agents may target these transcription factors similarly to what is currently studied for cancer and Parkinson's disease. Our second goal (Specific Aim 2) is in parallel to analyze the hypothalamic POMC expression profiles during alcohol drinking that characterize an underlying mechanism. We will determine if region-specific POMC changes occur in the hypothalamus after DID or CED drinking, or CPP. The study may reveal potentially new molecular mechanisms that provide new insights for understanding the molecular basis of alcohol-related disorders and novel targets for intervention in alcoholism.
期刊论文(8)
专著(0)
科研奖励(0)
会议论文
Modulation of proopiomelanocortin gene expression by ethanol in mouse anterior pituitary corticotrope tumor cell AtT20.
乙醇对小鼠垂体前叶皮质激素肿瘤细胞 AtT20 中阿片黑皮质素原基因表达的调节。
DOI: 10.1016/j.regpep.2014.07.002
发表时间: 2014
期刊: Regulatory peptides
影响因子: --
作者: [Zhou,Yan, Lapingo,Christina]
通讯作者: Lapingo,Christina
DOI: 10.13188/2327-204x.1000032
发表时间: 2022-05
期刊: Journal of pharmaceutics & pharmacology
影响因子: --
作者: [Zhou, Y, Zhou, D C, Kreek, M J]
通讯作者: Kreek, M J
mTORC1 pathway is involved in the kappa opioid receptor activation-induced increase in excessive alcohol drinking in mice.
mTORC1 通路参与 kappa 阿片受体激活诱导的小鼠过度饮酒增加。
DOI: 10.1016/j.pbb.2020.172954
发表时间: 2020
期刊: Pharmacology, biochemistry, and behavior
影响因子: --
作者: [Zhou,Yan, Liang,Yupu, Kreek,MaryJeanne]
通讯作者: Kreek,MaryJeanne
Clinically utilized kappa-opioid receptor agonist nalfurafine combined with low-dose naltrexone prevents alcohol relapse-like drinking in male and female mice.
临床上使用的κ阿片受体激动剂纳芙拉芬与低剂量纳曲酮联合使用可预防雄性和雌性小鼠的酒精复发样饮酒。
DOI: 10.1016/j.brainres.2019.146410
发表时间: 2019
期刊: Brain research
影响因子: 2.9
作者: [Zhou,Yan, Kreek,MaryJeanne]
通讯作者: Kreek,MaryJeanne
6
    RAPID POINT OF CARE TESTS FOR TUBERCULOSIS
    • 批准号:
      10497326
    • 项目类别:
    • 资助金额:
      $150.0万
    • 财政年份:
      2021
    • 负责人:
      YAN ZHOU
    • 依托单位:
    EFFECTS OF DRUGS OF ABUSE ON STRESS RESPONSIVE BRAIN SYSTEMS AND HYPOTHALAMIC...
    • 批准号:
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    • 项目类别:
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    • 财政年份:
      2007
    • 负责人:
      YAN ZHOU
    • 依托单位:
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    海外基金