The neurokinin-1 receptor mediates escalated alcohol intake induced by multiple drinking models.
The neurokinin-1 receptor mediates escalated alcohol intake induced by multiple drinking models.
复制标题
神经激肽-1 受体介导多种饮酒模型诱导的酒精摄入量增加。
DOI：
10.1016/j.neuropharm.2018.05.005
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发表时间：
2018
影响因子：
4.7
通讯作者：
Schank,JesseR
中科院分区：
文献类型：
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作者：
Sequeira,MichelleK;Nelson,BrittaS;Fulenwider,HannahD;King,CourtneyE;Nennig,SadieE;Bohannon,JenniferB;Cheng,Kejun;Rice,KennerC;Heilig,Markus;Schank,JesseR
我们以前已经证明，神经激肽-1受体（NK 1 R）是上调的中央核杏仁核的酒精偏好（P）的大鼠，这种受体介导的酒精消费量在这个应变。然而，目前尚不清楚非遗传的消费升级模型是否也由NK 1 R信号传导介导，如果是这样，那么是什么大脑区域控制这种效应。在这里提出的实验中，我们使用两种方法诱导升级的酒精摄入量远交Wistar大鼠：育亨宾预处理和间歇性酒精访问（周一，周三和周五的可用性; 20%的酒精）。我们发现，逐步增加的酒精消费量诱导育亨宾注射和间歇访问是衰减的NK 1 R拮抗剂L 822429的全身给药。此外，当连续酒精访问或访问单独的水相比，NK 1 R的表达增加，在脑桥核（NAC）和背侧纹状体，但不是杏仁核。当NK 1 R拮抗剂L 822429直接注入背侧纹状体时，间歇性访问引起的消耗量增加会减弱，但注入NAC时则不会。综上所述，这些结果表明，NK 1 R上调有助于酒精消费量的增加，这是由遗传选择，育亨宾注射和间歇性访问引起的。然而，这些行为所涉及的区域之间存在分离，杏仁核上调有助于增加消费的遗传易感性，而纹状体上调驱动环境暴露引起的升级。
We have previously demonstrated that the neurokinin-1 receptor (NK1R) is upregulated in the central nucleus of the amygdala of alcohol preferring (P) rats and that this receptor mediates escalated alcohol consumption in this strain. However, it is unclear if non-genetic models of escalated consumption are also mediated by NK1R signaling, and if so, what brain regions govern this effect. In the experiments presented here, we use two methods of inducing escalated alcohol intake in outbred Wistar rats: yohimbine pretreatment and intermittent alcohol access (Monday, Wednesday, and Friday availability; 20% alcohol). We found that escalated alcohol consumption induced by both yohimbine injection and intermittent access is attenuated by systemic administration of the NK1R antagonist L822429. Also, when compared to continuous alcohol access or access to water alone, NK1R expression was increased in the nucleus accumbens (NAC) and dorsal striatum, but not the amygdala. Escalated consumption induced by intermittent access was attenuated when the NK1R antagonist L822429 was infused directly into the dorsal striatum, but not when infused into the NAC. Taken together, these results suggest that NK1R upregulation contributes to escalated alcohol consumption that is induced by genetic selection, yohimbine injection, and intermittent access. However there is a dissociation between the regions involved in these behaviors with amygdalar upregulation contributing to genetic predisposition to escalated consumption and striatal upregulation driving escalation that is induced by environmental exposures.