Escalated Alcohol Self-Administration and Sensitivity to Yohimbine-Induced Reinstatement in Alcohol Preferring Rats: Potential Role of Neurokinin-1 Receptors in the Amygdala.
Escalated Alcohol Self-Administration and Sensitivity to Yohimbine-Induced Reinstatement in Alcohol Preferring Rats: Potential Role of Neurokinin-1 Receptors in the Amygdala.
复制标题
酒精偏好大鼠自我给药的逐步升级和对育亨宾诱导恢复的敏感性：杏仁核中 Neurokinin-1 受体的潜在作用。
DOI：
10.1016/j.neuroscience.2019.06.023
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发表时间：
2019
期刊：
影响因子：
3.3
通讯作者：
Schank,JesseR
中科院分区：
文献类型：
--
作者：
Nelson,BrittaS;Fulenwider,HannahD;Nennig,SadieE;Smith,BritessiaM;Sequeira,MichelleK;Chimberoff,ScottH;Richie,ChristopherT;Cheng,Kejun;Rice,KennerC;Harvey,BrandonK;Heilig,Markus;Schank,JesseR
遗传因素对酒精中毒的风险有很大的影响。为了研究这些因素和其他相关的表型，啮齿动物品系已经开发使用选择性育种高酒精偏好。其中一种模型，酒精偏好（P）大鼠，在过去几十年中已被用于数百项临床前研究。然而，很少有研究检查这种大鼠品系的复发样行为。在这项研究中，我们使用操作性自我管理和育亨宾诱导的复吸模型，以检查复发样行为P大鼠。我们以前的工作已经证明，P大鼠杏仁核（CeA）的神经激肽-1受体（NK 1 R）的表达增加，这在功能上有助于在这个应变升级的酒精消费。我们假设P大鼠对育亨宾诱导的恢复敏感性增加，这也是由CeA中的NK 1 R介导的。使用Fos染色，NK 1 R拮抗剂的位点特异性输注，和病毒载体过表达，我们研究了NK 1 R对育亨宾诱导的酒精寻求恢复的敏感性的影响。我们发现，P大鼠表现出增加的敏感性育亨宾诱导的恢复，以及增加的神经元激活后，育亨宾注射与对照组相比，Wistar品系的CeA。CeA内输注NK 1 R拮抗剂减弱育亨宾诱导的P大鼠恢复。相反，上调NK 1 R的Wistar大鼠CeA内增加酒精消耗和敏感性育亨宾诱导的恢复。这些研究结果表明，NK 1 R在CeA的上调有助于多种酒精相关的表型在P大鼠，包括饮酒和复发的敏感性。
Genetic factors significantly contribute to the risk for developing alcoholism. To study these factors and other associated phenotypes, rodent lines have been developed using selective breeding for high alcohol preference. One of these models, the alcohol preferring (P) rat, has been used in hundreds of preclinical studies over the last few decades. However, very few studies have examined relapse-like behavior in this rat strain. In this study, we used operant self-administration and yohimbine-induced reinstatement models to examine relapse-like behavior in P rats. Our previous work has demonstrated that P rats show increased expression of the neurokinin-1 receptor (NK1R) in the central nucleus of the amygdala (CeA), and this functionally contributes to escalated alcohol consumption in this strain. We hypothesized that P rats would show increased sensitivity to yohimbine-induced reinstatement that is also mediated by NK1R in the CeA. Using Fos staining, site-specific infusion of NK1R antagonist, and viral vector overexpression, we examined the influence of NK1R on the sensitivity to yohimbine-induced reinstatement of alcohol seeking. We found that P rats displayed increased sensitivity to yohimbine-induced reinstatement as well as increased neuronal activation in the CeA after yohimbine injection compared to the control Wistar strain. Intra-CeA infusion of NK1R antagonist attenuates yohimbine-induced reinstatement in P rats. Conversely, upregulation of NK1R within the CeA of Wistar rats increases alcohol consumption and sensitivity to yohimbine-induced reinstatement. These findings suggest that NK1R upregulation in the CeA contributes to multiple alcohol-related phenotypes in the P rat, including alcohol consumption and sensitivity to relapse.