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.
Università degli Studi di Teramo, Teramo, Italy.
Behav Brain Res. 2020 Feb 17;380:112445. doi: 10.1016/j.bbr.2019.112445. Epub 2019 Dec 19.
Ethanol use is widespread in adolescents, yet only some transition to problematic drinking. It is important to understand why the risk for problematic drinking varies across sub-groups of adolescents. This study reports a short-term selection program to generate Wistar rat lines (high and low adolescent ethanol drinking, ADHI and ADLO lines, respectively) that significantly differ in ethanol drinking at adolescence. The S generation and filial generations 1 (S), S, and S of ADHI and ADLO offspring were tested for basal or stress-induced ethanol intake at adulthood, or for shelter-seeking and risk-taking in the multivariate concentric square field test (MSCF). The study generated lines with significant differences in free-choice ethanol drinking at adolescence. The effects of the selection were observed at adulthood, beyond the stage in which the selection was conducted: S-ADHI but not S-ADLO adult male rats exhibited stress-induced drinking. These effects were associated with significant alterations in shelter-seeking and risk-taking behaviors. ADHI rats spent significantly less time in areas of the MSCF whose exploration entails risk-taking and significantly more time in dark, sheltered areas. Some of these effects were normalized by the administration of 0.5 g/kg ethanol. There were no line differences in ethanol-induced latency to lose the righting reflex or sleep time. These findings indicate that genetic risk of enhanced ethanol intake at adolescence is still present at adulthood, long after the developmental window when the selective breeding occurred. Exposure to stress at adulthood triggers the vulnerability associated with this genetic risk, an effect associated with enhanced anxiety.
乙醇在青少年中广泛使用,但只有一部分人会过渡到酗酒。了解为什么酗酒的风险在青少年亚群中有所不同非常重要。本研究报告了一个短期选择计划,以产生 Wistar 大鼠品系(高和低青少年乙醇饮用,ADHI 和 ADLO 品系,分别),这些品系在青少年时期的乙醇饮用量上有显著差异。ADHI 和 ADLO 后代的 S 代和 F1(S1、S2 和 S3)代进行了基础或应激诱导的成年期乙醇摄入测试,或进行了避难所寻求和风险承担的多维同心方形场测试(MSCF)。该研究生成了在青少年时期自由选择乙醇饮用方面具有显著差异的品系。选择的效果在成年期观察到,超出了选择进行的阶段:S-ADHI 而不是 S-ADLO 成年雄性大鼠表现出应激诱导的饮酒。这些影响与避难所寻求和风险承担行为的显著改变有关。ADHI 大鼠在 MSCF 的某些区域停留的时间明显减少,这些区域的探索需要承担风险,而在黑暗、遮蔽的区域停留的时间明显增加。这些影响中的一些通过给予 0.5 g/kg 乙醇得到了正常化。在乙醇诱导的翻正反射潜伏期或睡眠时间方面,没有系间差异。这些发现表明,青少年时期乙醇摄入增加的遗传风险在成年期仍然存在,远远超出了选择性繁殖发生的发育窗口期。成年期的应激暴露会引发与这种遗传风险相关的脆弱性,这种影响与焦虑增强有关。