Department of Pharmaceutical Biosciences, Neuropharmacology, Addiction & Behaviour, Uppsala University, Uppsala, Sweden.
Brain Res. 2011 Aug 8;1405:57-68. doi: 10.1016/j.brainres.2011.06.031. Epub 2011 Jul 8.
Some individuals control their ethanol consumption throughout life, but others escalate their intake to levels that increase the risk for addiction. The early environment influences the individual response to ethanol and affects the underlying physiological processes that lead to a transition from a voluntary to a compulsive use of ethanol. However, the neurobiological substrates for these processes are not understood. The present study aimed to test the hypothesis that early environmental experiences affect the neurobiological effects that are induced by voluntary ethanol consumption. Rat pups were subjected to three different rearing environments: conventional animal facility rearing or separation from dam and littermates for either 15 or 360min. In adulthood, the rats were exposed to a two-bottle free choice between ethanol and water for seven weeks. Tissue levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites were measured in brain areas that have been implicated in reward and addiction processes. Differences in ethanol-induced effects were noted in 5-HT-related measurements in the nucleus accumbens and ventral tegmental area and in dopamine-related measurements in the dorsal raphe nucleus (DRN). These results provided evidence of an early environmental impact on interactive neuronal circuits between the DRN and reward pathways. The amygdala, a key area in addiction processes, was particularly sensitive to early-life conditions. The animals that experienced the longest separation differed from the others; they had low basal 5-HT levels and responded with an increase in 5-HT after ethanol. These altered responses to initial ethanol consumption as a result of early environmental factors may affect the transition from habitual to compulsive drinking and contribute to individual vulnerability or resilience to addiction.
一些人可以控制一生的酒精摄入量,但另一些人则会逐渐增加摄入量,增加成瘾的风险。早期环境会影响个体对乙醇的反应,并影响导致从自愿使用乙醇向强迫性使用乙醇转变的潜在生理过程。然而,这些过程的神经生物学基础尚不清楚。本研究旨在检验以下假设:早期环境经历会影响自愿饮酒所诱导的神经生物学效应。幼鼠经历三种不同的饲养环境:常规动物饲养设施或与母鼠和同窝幼鼠分离 15 或 360 分钟。成年后,这些大鼠在七周内被暴露于自由选择两瓶水和乙醇的环境中。在大脑中与奖励和成瘾过程相关的区域测量了多巴胺、5-羟色胺(5-HT)及其代谢物的组织水平。在伏隔核和腹侧被盖区的 5-HT 相关测量以及中缝背核(DRN)的多巴胺相关测量中,注意到了乙醇诱导效应的差异。这些结果提供了早期环境对 DRN 和奖励途径之间相互作用神经元回路影响的证据。杏仁核是成瘾过程中的一个关键区域,对早期生活条件特别敏感。经历最长分离的动物与其他动物不同;它们的基础 5-HT 水平较低,并且在乙醇后 5-HT 水平升高。由于早期环境因素导致的对初始乙醇消耗的这些改变的反应可能会影响从习惯性饮酒到强迫性饮酒的转变,并导致个体对成瘾的易感性或弹性。