Kappa opioid receptor and dynorphin signaling in the central amygdala regulates alcohol intake.
Kappa opioid receptor and dynorphin signaling in the central amygdala regulates alcohol intake.
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中央杏仁核中的Kappa阿片受体和强啡肽信号调节酒精摄入量。
DOI：
10.1038/s41380-020-0690-z
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发表时间：
2021-06
影响因子：
11
通讯作者：
Kash TL
中科院分区：
文献类型：
--
作者：
Bloodgood DW;Hardaway JA;Stanhope CM;Pati D;Pina MM;Neira S;Desai S;Boyt KM;Palmiter RD;Kash TL
过量饮酒已被证明会改变大脑回路，使个体易于在未来滥用酒精。先前的研究表明杏仁核中央核（CeA）是介导戒断症状和调节酒精摄入的重要部位。此外，最近的工作已经确定了κ阿片受体（KOR）及其内源性配体强啡肽在介导这些过程中的作用。然而，目前尚不清楚这些影响是否是由于强啡肽或KOR产生的CeA本身或其他输入脑区。为了直接研究前强啡肽原（PDYN）和KOR表达在CeA神经元中的作用，我们对这些基因进行了区域特异性条件性敲除，并评估了对黑暗中饮酒（DID）和间歇性访问（IA）范式的影响。条件基因敲除导致性别特异性反应，其中PDYN敲除减少了雄性和雌性小鼠的饮酒，而KOR敲除仅减少了雄性小鼠的饮酒。我们还发现，PDYN和KOR基因敲除都不能防止饮酒引起的焦虑。最后，饮酒的历史并没有改变突触传递的PDYN神经元在CeA的任何性别，但PDYN神经元的兴奋性增加，在雄性小鼠。综上所述，我们的研究结果表明，PDYN和KOR信号在CeA中发挥着重要作用，在调节过度饮酒，并强调需要未来的研究，以研究这是如何介导的下游效应区域。
Excessive alcohol drinking has been shown to modify brain circuitry to predispose individuals for future alcohol abuse. Previous studies have implicated the central nucleus of the amygdala (CeA) as an important site for mediating the somatic symptoms of withdrawal and for regulating alcohol intake. In addition, recent work has established a role for both the Kappa Opioid Receptor (KOR) and its endogenous ligand dynorphin in mediating these processes. However, it is unclear whether these effects are due to dynorphin or KOR arising from within the CeA itself or other input brain regions. To directly examine the role of preprodynorphin (PDYN) and KOR expression in CeA neurons, we performed region-specific conditional knockout of these genes and assessed the effects on the Drinking in the Dark (DID) and Intermittent Access (IA) paradigms. Conditional gene knockout resulted in sex-specific responses wherein PDYN knockout decreased alcohol drinking in both male and female mice, whereas KOR knockout decreased drinking in males only. We also found that neither PDYN nor KOR knockout protected against anxiety caused by alcohol drinking. Lastly, a history of alcohol drinking did not alter synaptic transmission in PDYN neurons in the CeA of either sex, but excitability of PDYN neurons was increased in male mice only. Taken together, our findings indicate that PDYN and KOR signaling in the CeA plays an important role in regulating excessive alcohol consumption and highlight the need for future studies to examine how this is mediated through downstream effector regions.
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酒精中毒的一二拳：中央杏仁核的作用/kappa-阿片受体。
影响因子：
10.6
作者：
Kissler, Jessica L.;Sirohi, Sunil;Reis, Daniel J.;Jansen, Heiko T.;Quock, Raymond M.;Smith, Daniel G.;Walker, Brendan M.
通讯作者：
Walker, Brendan M.
DOI：
10.1111/acer.12145
发表时间：
2013-10
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Cox BR;Olney JJ;Lowery-Gionta EG;Sprow GM;Rinker JA;Navarro M;Kash TL;Thiele TE
通讯作者：
Thiele TE
影响因子：
7.3
作者：
Ho JH;Stahl EL;Schmid CL;Scarry SM;Aubé J;Bohn LM
通讯作者：
Bohn LM
影响因子：
16.6
作者：
de Guglielmo, Giordano;Kallupi, Marsida;George, Olivier
通讯作者：
George, Olivier
影响因子：
4.7
作者：
Erikson CM;Wei G;Walker BM
通讯作者：
Walker BM