Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumption.
Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumption.
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DOI：
10.1016/j.pbb.2022.173377
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发表时间：
2022-05
影响因子：
3.6
通讯作者：
van Rijn, Richard M.
中科院分区：
文献类型：
--
作者：
French, Alexander R.;Gutridge, Anna M.;Yuan, Jinling;Royer, Q. Hawk;van Rijn, Richard M.
κ阿片受体是一种已知的乙醇消耗调节剂，但其作用背后的分子机制尚未得到充分研究。支架蛋白β-arrestin 2先前已涉及在相关δ阿片受体处驱动乙醇消耗，并且也被认为是其他负性κ阿片受体介导的效应背后的驱动因素。在这里，我们使用具有不同功效的κ阿片激动剂招募β-arrestin 2和敲除动物，以确定β-arrestin 2是否在κ阿片受体调节自愿乙醇消耗中发挥作用。我们发现具有低β-抑制蛋白2功效的激动剂比具有高β-抑制蛋白2功效的激动剂更一致地降低乙醇消耗。然而，β-arrestin 2的敲低放大了arrestin募集κ激动剂U 50，488和纳呋拉芬的乙醇消耗促进作用。我们控制了κ阿片受体的潜在混淆镇静作用，发现β-arrestin 2不是κ阿片受体介导的镇静作用所必需的，并且镇静作用与对乙醇消耗的影响无关。总的来说，结果表明，激动剂，性别和κ阿片受体调节乙醇消耗之间的复杂关系，κ阿片受体介导的镇静作用很小。
The kappa opioid receptor is a known regulator of ethanol consumption, but the molecular mechanisms behind its actions have been underexplored. The scaffolding protein β-arrestin 2 has previously been implicated in driving ethanol consumption at the related delta opioid receptor and has also been suggested to be a driver behind other negative kappa opioid receptor mediated effects. Here, we used kappa opioid agonists with different efficacies for recruiting β-arrestin 2 and knockout animals to determine whether there is a role for β-arrestin 2 in the modulation of voluntary ethanol consumption by the kappa opioid receptor. We find that an agonist with low β-arrestin 2 efficacy more consistently lowers ethanol consumption than agonists with high efficacy for β-arrestin 2. However, knockdown of β-arrestin 2 amplifies the ethanol consumption-promoting effects of the arrestin-recruiting kappa agonists U50,488 and nalfurafine. We control for potentially confounding sedative effects at the kappa opioid receptor and find that β-arrestin 2 is not necessary for kappa opioid receptor-mediated sedation, and that sedation does not correlate with effects on ethanol consumption. Overall, the results suggest a complex relationship between agonist profile, sex, and kappa opioid receptor modulation of ethanol consumption, with little role for kappa opioid receptor-mediated sedation.
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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.
影响因子：
--
作者：
Banks ML
通讯作者：
Banks ML
影响因子：
3.4
作者：
Bruchas, Michael R.;Chavkin, Charles
通讯作者：
Chavkin, Charles
影响因子：
3.1
作者：
Lim, Jana P.;Zou, Mimi E.;Janak, Patricia H.;Messing, Robert O.
通讯作者：
Messing, Robert O.
影响因子：
5.3
作者：
Abraham, Antony D.;Schattauer, Selena S.;Chavkin, Charles
通讯作者：
Chavkin, Charles