Grupo de Neurociencias, Laboratorio de Canabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.
Grupo de Neurociencias, Laboratorio de Neurogenómica Cognitiva, Departamento de Psicofisiología, Facultad de Psicología, Universidad Nacional Autónoma de México, Mexico.
Brain Res. 2019 Dec 15;1725:146485. doi: 10.1016/j.brainres.2019.146485. Epub 2019 Sep 27.
Abusive alcohol consumption is a health problem, worldwide. There is extensive literature indicating that cannabinoid 1 receptor (CB1R) plays a crucial role in mediating alcohol's reward effects. Maternal care deprivation (MCD) is a reliable rodent model of early life stress that leads to high levels of anxiety and alterations in motivation, which may increase vulnerability to alcohol consumption. The present study researched whether anxiety-like behaviors and the level of motivation for a natural reward, and CB1R expression in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) can predict alcohol consumption in non-MCD and MCD male rats. Results indicate that MCD increases anxiety-like behaviors, i.e., reduces time in open arms in the elevated plus maze and increases alcohol intake. In turn, the motivation for a palatable reward, i.e., a chocolate flavored pellet, was not affected by MCD. MCD reduces CB1R expression in the PFC and increases it in the NAcc. Hence, both higher anxiety-like behaviors and higher CB1R expression in the NAcc and lower CB1R expression in the PFC are associated with higher alcohol intake. These results suggest that early life adverse experiences induce a reprogramming of the brain's endocannabinoid system that very likely contributes to making the brain vulnerable to develop alcohol abuse and dependence.
酗酒是一个全球性的健康问题。有大量文献表明,大麻素 1 型受体(CB1R)在介导酒精的奖赏效应中起着至关重要的作用。母体剥夺(MCD)是一种可靠的早期生活应激啮齿动物模型,会导致高水平的焦虑和动机改变,从而增加对酒精消费的易感性。本研究旨在研究焦虑样行为和对自然奖赏的动机水平,以及前额叶皮层(PFC)和伏隔核(NAcc)中的 CB1R 表达是否可以预测非 MCD 和 MCD 雄性大鼠的酒精消费。结果表明,MCD 增加了焦虑样行为,即减少了高架十字迷宫中开放臂的时间,并增加了酒精摄入量。相反,对美味奖励(即巧克力味丸)的动机不受 MCD 的影响。MCD 降低了 PFC 中的 CB1R 表达,增加了 NAcc 中的 CB1R 表达。因此,较高的焦虑样行为和 NAcc 中较高的 CB1R 表达以及 PFC 中较低的 CB1R 表达与较高的酒精摄入量相关。这些结果表明,早期生活中的不良经历会导致大脑内源性大麻素系统的重新编程,这很可能导致大脑易患酒精滥用和依赖。