权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of pro-opiomelanocortin neuronal circuitry in mediating ethanol consumption

阿片黑皮质素原神经元回路在介导乙醇消耗中的作用

基本信息

批准号：
10224860
负责人：
Jonna M Jackson
金额：
$ 6.86万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224860
关键词：
Alcohol abuse Alcohol consumption Amino Acid Neurotransmitters Amino Acids Amygdaloid structure Animals Area Cell physiology Cells Confocal Microscopy Development Electrophysiology (science)Endorphins Ethanol FOS gene Feeding behaviors Glutamates Goals Hypothalamic structure Immunoblot Analysis Immunohistochemistry In Vitro Laboratories Lead Link Measures Mediating Methodology Modification Molecular Motivation N-Methylaspartate Naltrexone Neurobiology Neurons Nucleus Accumbens Opioid Antagonist Pathway interactions Pattern Peptides Pharmaceutical Preparations Physiological Pro-Opiomelanocortin Property Public Health Research Rewards Role Series Structure of nucleus infundibularis hypothalami System Techniques Testing Time Training Transgenic Mice United States Ventral Tegmental Area Western Blotting alcohol abuse therapy alcohol behavior alcohol use disorder alcohol-related death alpha-Melanocyte stimulating hormone anatomical tracing base behavior test beta-Endorphin cell type designer receptors exclusively activated by designer drugs drinking drug of abuse endogenous opioids experimental study gamma-Aminobutyric Acid improved in vivo neural circuit neuronal circuitry novel novel strategies relating to nervous system

项目摘要

Project Abstract Alcohol abuse is a worldwide public health concern and leads to an estimated 90,000 alcohol-related deaths in the United States annually. Recent evidence suggests that ethanol may promote its euphoric and motivational effects, in part, by activating the endogenous opioid system. Further supporting the role of the endogenous opioid system in alcohol abuse, one of the most frequently utilized medications for treating alcohol use disorders to date is naltrexone, a broad spectrum opioid receptor antagonist. One particular circuit of the endogenous opioid system consists of pro-opiomelanocortin (POMC) producing neurons in the arcuate nucleus (ArcN) of the hypothalamus, which project heavily to reward-related areas such as the ventral tegmental area (VTA), nucleus accumbens (NAc) and amygdala (Amy). These neurons utilize POMC-derived neuroactive peptides, such as β- endorphin (B-END), in conjunction with amino acid transmitters to regulate their local and extrahypothalamic targets. Based on this utilization of neuroactive peptides as well as excitatory and inhibitory co-transmitters, it is likely that POMC neurons can differentially regulate their local and extrahypothalamic targets. Ethanol administration induces B-END release in the NAc, which is thought to underlie the reinforcing properties and motivational behaviors of alcohol. The overarching goal of this proposal is to test the hypothesis that POMC- expressing neurons of the hypothalamus are directly involved in regulating ethanol consumption. These results will broaden the scope of our current understanding of the neural basis of ethanol intake and its potential relevance to alcohol abuse. Thus, I propose to examine the role of POMC circuitry originating in the ArcN of the hypothalamus in modulating ethanol consumption via bidirectional chemogenetic manipulation. Specifically, I hypothesize that activation of local POMC circuitry within the ArcN will promote ethanol consumption and that activation of POMC-expressing neurons will lead to increased levels of β-endorphin within the hypothalamus and its reward-related target regions (the NAc, VTA and Amy). Additionally, I aim to determine circuit-specific activation of POMC neuronal projections following ethanol consumption, where I predict that ethanol will have preferential activation of POMC-expressing neurons projecting to the NAc and VTA. Ultimately, these studies will advance the current understanding of ethanol-mediated effects on the endogenous opioid system and may lead to novel approaches to better treat alcohol abuse. Through these proposed studies, I will be trained in in vivo chemogenetics, animal behavioral testing, anatomical tracing, immunohistochemistry, western blot analysis and confocal microscopy.

项目摘要

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Alcohol consumption preferentially activates a subset of pro-opiomelanocortin (POMC) producing neurons targeting the amygdala.

DOI：
10.1016/j.neuropharm.2021.108674
发表时间：
2021-09-01
期刊：
Neuropharmacology
影响因子：
4.7
作者：
Leyrer-Jackson JM;Hood LE;Olive MF
通讯作者：
Olive MF

Metabotropic glutamate receptors and cognition: From underlying plasticity and neuroprotection to cognitive disorders and therapeutic targets.

代谢型谷氨酸受体和认知：从潜在的可塑性和神经保护到认知障碍和治疗目标。

DOI：
10.1016/bs.irn.2022.10.004
发表时间：
2023
期刊：
International review of neurobiology
影响因子：
0
作者：
Hoglund,BrandonK;Carfagno,Vincent;Olive,MFoster;Leyrer-Jackson,JonnaM
通讯作者：
Leyrer-Jackson,JonnaM

Sex differences and the lack of effects of chemogenetic manipulation of pro-opiomelanocortin (POMC) neurons on alcohol consumption in male and female mice.

DOI：
10.1016/j.brainres.2022.147901
发表时间：
2022-07-01
期刊：
Brain research
影响因子：
2.9
作者：
通讯作者：

Ethanol consumption activates a subset of arcuate nucleus pro-opiomelanocortin (POMC)-producing neurons: a c-fos immunohistochemistry study.

DOI：
10.14814/phy2.15231
发表时间：
2022-03
期刊：
Physiological reports
影响因子：
2.5
作者：
Hood LE;Nagy EK;Leyrer-Jackson JM;Olive MF
通讯作者：
Olive MF

A line before liquor: a novel model of cocaine and alcohol co-abuse reveals changes in glutamate homeostasis.

酒前一行：可卡因和酒精共同滥用的新模型揭示了谷氨酸稳态的变化。

DOI：
10.1038/s41386-019-0470-0
发表时间：
2020
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Leyrer-Jackson,JonnaM;Olive,MFoster
通讯作者：
Olive,MFoster