Sigma receptor-induced heavy drinking in rats: Modulation by the opioid receptor system.
Sigma receptor-induced heavy drinking in rats: Modulation by the opioid receptor system.
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DOI：
10.1016/j.pbb.2020.172914
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发表时间：
2020-05
影响因子：
3.6
通讯作者：
Sabino, Valentina
中科院分区：
文献类型：
--
作者：
Valenza, Marta;Blasio, Angelo;DiLeo, Alyssa;Cottone, Pietro;Sabino, Valentina
酒精使用障碍（AUD）是世界范围内发病率和死亡率的主要原因，因此需要新的有效治疗方法。阿片受体系统是酒精奖赏效应的介导者;特别是，μ阿片受体的激活增强了啮齿动物的乙醇摄入，阿片受体拮抗剂如纳洛酮和纳洛酮降低了其愉悦和强化作用，从而减少了酒精。σ受体（Sig-Rs）已被提出作为酒精作用的调节剂，因此，作为AUD的潜在新药理学靶点。与μ阿片配体类似，SigR激动剂增加了过量饮酒动物模型中的酒精摄入，而SigR拮抗剂减少了酒精摄入。然而，这两个受体系统之间的潜在串扰与酒精消费迄今尚未调查。在这里，我们解决了这个问题，通过测试激活或抑制阿片受体对酒精偏好大鼠的SigR慢性刺激诱导的大量饮酒的影响。我们发现，阿片受体激动剂吗啡，其本身增加乙醇摄入量，在亚阈值剂量下减少了由SigR激动剂1，3-二邻甲苯基胍（DTG）重复治疗诱导的暴食样饮酒;相反，阿片受体拮抗剂纳曲酮，其本身减少乙醇摄入量，在亚阈值剂量下增强DTG诱导的暴食样饮酒。我们的数据显示了阿片类药物和SigR系统之间的串扰与饮酒的调节有关，这为AUD的神经生物学提供了重要的见解，并可能导致开发新的治疗方法，无论是单独的还是联合的。
Alcohol use disorder (AUD) is a major cause of morbidity and mortality worldwide, for which new efficacious treatments are necessary. The opioid receptor system is a mediator of the rewarding effects of alcohol; in particular, while activation of μ opioid receptors enhances ethanol intake in rodents, opioid-receptor antagonists, such as naloxone and naltrexone, reduce its pleasurable and reinforcing effects, thereby decreasing alcohol. Sigma receptors (Sig-Rs) have been proposed as modulators of the effects of alcohol and, therefore, as a potential new pharmacological target for AUD. Somewhat analogously to μ opioid ligands, SigR agonists increase, while SigR antagonists decrease alcohol intake in animal models of excessive alcohol drinking. However, a potential cross-talk between these two receptor systems in relation to alcohol consumption has so far not been investigated. Here, we addressed this question pharmacologically, by testing the effects of either activating or inhibiting opioid receptors on the heavy alcohol drinking induced by chronic stimulation of SigR in alcohol-preferring rats. We found that the opioid receptor agonist morphine, which per se increases ethanol intake, at a sub-threshold dose reduces the binge-like drinking induced by the repeated treatment with the SigR agonist 1,3-di-o-tolylguanidine (DTG); conversely, the opioid receptor antagonist naltrexone, which per se reduces ethanol intake, at a sub-threshold dose potentiates the DTG-induced binge-like drinking. Our data show a cross-talk between the opioid and SigR systems relevant to the modulation of alcohol drinking, which provides important insights into the neurobiology of AUD and may lead to the development of novel therapies, either standalone or in combination.
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影响因子：
10.6
作者：
Garces-Ramirez, Linda;Green, Jennifer L.;Hiranita, Takato;Kopajtic, Theresa A.;Mereu, Maddalena;Thomas, Alexandra M.;Mesangeau, Christophe;Narayanan, Sanju;McCurdy, Christopher R.;Katz, Jonathan L.;Tanda, Gianluigi
通讯作者：
Tanda, Gianluigi
影响因子：
1.6
作者：
Bhutada, Pravinkumar S.;Mundhada, Yogita R.;Umathe, Sudhir N.
通讯作者：
Umathe, Sudhir N.
影响因子：
25.8
作者：
Grant BF;Goldstein RB;Saha TD;Chou SP;Jung J;Zhang H;Pickering RP;Ruan WJ;Smith SM;Huang B;Hasin DS
通讯作者：
Hasin DS
影响因子：
5
作者：
CECI, A;SMITH, M;FRENCH, ED
通讯作者：
FRENCH, ED
DOI：
10.1097/01.alc.0000075548.83053.a9
发表时间：
2003-07-01
影响因子：
3.2
作者：
Balldin, J;Berglund, M;Willander, A
通讯作者：
Willander, A