Sex differences and the lack of effects of chemogenetic manipulation of pro-opiomelanocortin (POMC) neurons on alcohol consumption in male and female mice.
Sex differences and the lack of effects of chemogenetic manipulation of pro-opiomelanocortin (POMC) neurons on alcohol consumption in male and female mice.
复制标题
性别差异和缺乏前阿黑皮素（POMC）神经元的化学遗传操作对雄性和雌性小鼠饮酒的影响。
DOI：
10.1016/j.brainres.2022.147901
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发表时间：
2022-07-01
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
内源性阿片系统与酒精的奖赏和增强作用有关。下丘脑弓状核内的阿片黑素皮质素原神经元分泌多种与饮酒有关的多肽，包括β-内啡肽(β-END)、促黑素细胞刺激素(α-α)和促肾上腺皮质激素(ACTH)。在这项研究中，我们利用化学遗传学对ArcN POMC神经元进行双向调节，以确定它们在酒精和糖精消耗中的作用以及POMC衍生多肽的区域水平。雄性和雌性POMC-cre小鼠被注入病毒载体或对照载体到ArcN中，所设计的病毒载体可依赖于兴奋性和抑制性DREADD的表达。恢复后，允许动物在黑暗中饮酒(DID)，连续4天暴饮式摄入糖精。在最后一次测试之前，动物被注射氯氮平-N-氧化物(2.5 mg/kg，i.p.)。用于DREADD激活。在最后一次DID会议后，动物被安乐死，解剖弓状核、VTA、杏仁核和NAC，并用免疫印迹法评估POMC多肽的表达。我们发现，在第2-4次实验中，雌性小鼠比雄性小鼠摄入更多的酒精，而化学生成激活对酒精或糖精的消耗没有任何影响。我们发现β-END在弓状核内的表达与饮酒呈正相关。鉴于ArcN POMC神经元的分子和功能异质性，未来的研究需要评估ArcN内这些神经元特定亚群的调节对酒精和糖精等奖赏物质消耗的影响。
The endogenous opioid system has been implicated in the rewarding and reinforcing effects of alcohol. Pro-opiomelanocortin (POMC) neurons located within the arcuate nucleus of the hypothalamus (ArcN) secrete multiple peptides associated with alcohol consumption, including β-endorphin (β-END), α-melanocyte stimulating hormone (α-MSH), and adrenocorticotropic hormone (ACTH). In this study, we utilized chemogenetics to bidirectionally modulate ArcN POMC neurons to determine their role in alcohol and saccharin consumption and regional levels of POMC-derived peptides. Male and female POMC-cre mice were infused with viral vectors designed for cre-dependent expression of either excitatory and inhibitory DREADDs or a control vector into the ArcN. Following recovery, animals were allowed to consume alcohol or saccharin using the drinking-in-the-dark (DID) paradigm of binge-like intake for 4 consecutive days. Prior to the final test session, animals were injected with clozapine-N-oxide (2.5 mg/kg, i.p.) for DREADD activation. Following the last DID session, animals were euthanized and the ArcN, VTA, amygdala and NAc were dissected and assessed for POMC peptide expression utilizing western blotting. We found that female mice consumed more alcohol than males during DID sessions 2–4, and that chemogenetic activation had no effect on alcohol or saccharin consumption in either sex. We found that β-END expression within the ArcN positively correlated with alcohol consumption. Given the molecular and functional heterogeneity of ArcN POMC neurons, future studies are needed to assess the effects of modulation of specific subpopulations of these neurons within the ArcN on consumption of rewarding substances such as alcohol and saccharin.
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影响因子：
29
作者：
Gómez-Valadés AG;Pozo M;Varela L;Boudjadja MB;Ramírez S;Chivite I;Eyre E;Haddad-Tóvolli R;Obri A;Milà-Guasch M;Altirriba J;Schneeberger M;Imbernón M;Garcia-Rendueles AR;Gama-Perez P;Rojo-Ruiz J;Rácz B;Alonso MT;Gomis R;Zorzano A;D'Agostino G;Alvarez CV;Nogueiras R;Garcia-Roves PM;Horvath TL;Claret M
通讯作者：
Claret M
影响因子：
5
作者：
BALSKUBIK, R;SHIPPENBERG, TS;HERZ, A
通讯作者：
HERZ, A
DOI：
10.1152/ajpheart.00411.2020
发表时间：
2020-11-01
影响因子：
4.8
作者：
Jiang, Jingwei;Morgan, Donald A.;Rahmouni, Kamal
通讯作者：
Rahmouni, Kamal
影响因子：
9.8
作者：
Jeong JH;Lee DK;Liu SM;Chua SC Jr;Schwartz GJ;Jo YH
通讯作者：
Jo YH
DOI：
10.15585/mmwr.mm6939a6
发表时间：
2020-10-02
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Esser MB;Sherk A;Liu Y;Naimi TS;Stockwell T;Stahre M;Kanny D;Landen M;Saitz R;Brewer RD
通讯作者：
Brewer RD