Effects of Ethanol Exposure During Adolescence or Adulthood on Locomotor Sensitization and Dopamine Levels in the Reward System
Effects of Ethanol Exposure During Adolescence or Adulthood on Locomotor Sensitization and Dopamine Levels in the Reward System
复制标题
DOI：
10.3389/fnbeh.2020.00031
复制
发表时间：
2020-03-06
影响因子：
3
通讯作者：
Camarini, Rosana
中科院分区：
文献类型：
--
作者：
Carrara-Nascimento, Priscila Fernandes;Hoffmann, Lucas Barbosa;Camarini, Rosana
行为敏感化是以运动行为逐渐增多为特征的神经适应过程。参与行为敏化的主要神经底物位于多巴胺能中皮质边缘通路，该通路在青春期仍处于发育阶段。为了研究酒精行为敏感化和奖赏系统不同脑区多巴胺水平的年龄差异，对青春期和成年小鼠重复给予生理盐水或乙醇(2.0g/kg ip)。连续15d，给药后5d用生理盐水或乙醇激发。用高效液相色谱法测定了前额叶皮质(PFC)、伏隔核(NAC)和纹状体组织中多巴胺及其代谢物的含量。虽然反复注射乙醇会导致成年和青少年小鼠的运动敏感化，但只有成年小鼠对随后的酒精刺激注射表现出敏化。神经化学结果显示，与成年人相比，青少年的多巴胺水平降低。具体地说，在青春期用乙醇预处理的小鼠，在酒精挑战注射后，与相应的成年组相比，PFC中的多巴胺水平较低，而青春期前的小鼠在急性乙醇处理后，与成人相比，在NAC中的多巴胺水平较低。这些发现表明，青春期小鼠不仅对酒精致敏表达的敏感性低于成年小鼠，而且酒精暴露后PFC和NAC中的多巴胺含量也较低。
Behavioral sensitization is a process of neuroadaptation characterized by a gradual increase in motor behaviors. The major neural substrates involved in the behavioral sensitization lie on the dopaminergic mesocorticolimbic pathway, which is still under development during adolescence. To investigate age-differences in ethanol behavioral sensitization and dopamine levels in distinct brain regions of the reward system, adolescent and adult mice were repeatedly pretreated with saline or ethanol (2.0 g/kg i.p.) during 15 consecutive days and challenged with saline or ethanol 5 days after pretreatment. Dopamine and its metabolites were measured in tissue samples of the prefrontal cortex (PFC), nucleus accumbens (NAc) and striatum by HPLC analysis. While repeated ethanol administration resulted in the development of locomotor sensitization in both adult and adolescent mice, only the adults expressed sensitization to a subsequent ethanol challenge injection. Neurochemical results showed reduced dopamine levels in adolescents compared to adults. Specifically, mice pretreated with ethanol during adolescence displayed lower dopamine levels in the PFC compared to the respective adult group in response to an ethanol challenge injection, and preadolescent mice exhibited lower dopamine levels in the NAc following an acute ethanol treatment compared to adults. These findings suggest that adolescent mice are not only less sensitive to the expression of ethanol-induced sensitization than adults, but also show lower dopamine content after ethanol exposition in the PFC and NAc.