Instituto de Investigación Médica M. y M. Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba, Córdoba C.P. 5000, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba C.P. 5000, Argentina.
Instituto de Investigación Médica M. y M. Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba, Córdoba C.P. 5000, Argentina.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):220-233. doi: 10.1016/j.pnpbp.2017.06.027. Epub 2017 Jun 27.
Alcohol use disorders are modulated by genetic factors, but the identification of specific genes and their concomitant biological changes that are associated with a higher risk for these disorders has proven difficult. Alterations in the sensitivity to the motivational effects of ethanol may be one way by which genes modulate the initiation and escalation of ethanol intake. Rats and mice have been selectively bred for high and low ethanol consumption during adulthood. However, selective breeding programs for ethanol intake have not focused on adolescence. This phase of development is associated with the initiation and escalation of ethanol intake and characterized by an increase in the sensitivity to ethanol's appetitive effects and a decrease in the sensitivity to ethanol's aversive effects compared with adulthood. The present study performed short-term behavioral selection to select rat lines that diverge in the expression of ethanol drinking during adolescence. A progenitor nucleus of Wistar rats (F) and filial generation 1 (F), F, and F adolescent rats were derived from parents that were selected for high (STDRHI) and low (STDRLO) ethanol consumption during adolescence and were tested for ethanol intake and responsivity to ethanol's motivational effects. STDRHI rats exhibited significantly greater ethanol intake and preference than STDRLO rats. Compared with STDRLO rats, STDRHI F and F rats exhibited a blunted response to ethanol in the conditioned taste aversion test. F and F STDRHI rats but not STDRLO rats exhibited ethanol-induced motor stimulation. STDRHI rats exhibited avoidance of the white compartment of the light-dark box, a reduction of locomotion, and a reduction of saccharin consumption, suggesting an anxiety-prone phenotype. The results suggest that the genetic risk for enhanced ethanol intake during adolescence is associated with lower sensitivity to the aversive effects of ethanol, heightened reactivity to ethanol's stimulating effects, and enhanced innate anxiety.
酒精使用障碍受遗传因素调节，但确定与这些障碍风险较高相关的特定基因及其伴随的生物学变化一直很困难。对乙醇的动机效应的敏感性的改变可能是基因调节乙醇摄入的起始和升级的一种方式。大鼠和小鼠已经被选择性繁殖，以在成年期产生高和低的乙醇消耗。然而，乙醇摄入的选择性繁殖计划并没有集中在青春期。这一发展阶段与乙醇摄入的起始和升级有关，其特征是对乙醇的食欲效应的敏感性增加，对乙醇的厌恶效应的敏感性降低，与成年期相比。本研究进行了短期行为选择，以选择在青春期乙醇饮用表现不同的大鼠品系。Wistar 大鼠的祖核（F）和第一代（F）、F 和 F 青春期大鼠来自于在青春期选择高（STDRHI）和低（STDRLO）乙醇消耗的父母，并对其进行了乙醇摄入和对乙醇动机效应的反应性测试。STDRHI 大鼠的乙醇摄入量和偏好明显高于 STDRLO 大鼠。与 STDRLO 大鼠相比，STDRHI F 和 F 大鼠在条件性味觉厌恶测试中对乙醇的反应迟钝。F 和 F STDRHI 大鼠而非 STDRLO 大鼠表现出乙醇诱导的运动刺激。STDRHI 大鼠表现出对明暗箱白色隔间的回避、运动减少和蔗糖消耗减少，提示焦虑倾向表型。结果表明，青春期乙醇摄入增加的遗传风险与对乙醇厌恶效应的敏感性降低、对乙醇刺激效应的反应性增强以及固有焦虑增强有关。
