González-Portilla Macarena, Montagud-Romero Sandra, Navarrete Francisco, Gasparyan Ani, Manzanares Jorge, Miñarro José, Rodríguez-Arias Marta
Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
Department of Psychology and Sociology, University of Zaragoza, C/ Ciudad Escolar s/n, 44003 Teruel, Spain.
Int J Mol Sci. 2021 May 17;22(10):5279. doi: 10.3390/ijms22105279.
Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.
酗酒（BD）和不良饮食习惯是许多青少年常见的两种行为，它们会使肠道微生物群朝着促炎方向改变。即使在肥胖症发作之前，饮酒和高脂饮食（HFD）后也会观察到肠道微生物群的失调变化。在本研究中，我们通过在小鼠中使用自我给药（SA）范式，研究青少年BD与持续或间歇性HFD联合时的神经炎症反应及其对成年小鼠乙醇摄入的影响。在BD后24小时、3周后以及乙醇（EtOH）自我给药后，在纹状体中测量炎症生物标志物IL-6和CX3CL1。青少年BD增加了口服SA中的酒精摄入量，并产生了更强的寻求该物质的动机。同样，间歇性接触HFD的小鼠表现出更高的EtOH摄入量，而持续接触HFD的小鼠则出现相反的效果。生化分析表明，在BD后及三周后，纹状体中IL-6和CX3CL1水平升高。此外，在生理盐水处理的小鼠中，持续接触HFD后CX3CL1增加。在口服SA程序后，仅在暴露于BD和HFD的动物中纹状体IL-6增加。此外，所有暴露于BD和HFD的组中纹状体CX3CL1水平均升高。总体而言，我们的研究结果表明，青少年BD和间歇性HFD会增加成年期酒精摄入量，并指出神经炎症是调节这种相互作用的重要机制。
