Montagud-Romero Sandra, Daza-Losada Manuel, Vidal-Infer Antonio, Maldonado Concepción, Aguilar María A, Miñarro Jose, Rodríguez-Arias Marta
Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain.
PLoS One. 2014 Mar 21;9(3):e92576. doi: 10.1371/journal.pone.0092576. eCollection 2014.
The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype.
本研究的目的是调查寻求新奇表型是否介导青春期间歇性乙醇中毒的长期后果。采用洞板试验将青春期小鼠分为高寻求新奇者或低寻求新奇者。随后,在14天的时间里,动物在48小时间隔的连续两天接受乙醇(1.25或2.5克/千克)。3周后,使用高架十字迷宫、自发运动活动和社交互动试验研究焦虑水平。另一组小鼠接受相同的程序,但仅接受2.5克/千克剂量的乙醇。3周后,为了诱导条件性位置偏好,对相同的动物给予1或6毫克/千克的可卡因或1或2.5毫克/千克的摇头丸。结果显示,高寻求新奇小鼠的攻击行为减少且具有抗焦虑特征,而低寻求新奇小鼠探索新物体的潜伏期更长。当用亚阈值剂量的药物诱导条件性位置偏好时,乙醇暴露增强了两组中可卡因和摇头丸的强化作用。仅在高寻求新奇动物中,在给予启动剂量后,消退的可卡因诱导的条件性位置偏好(1和6毫克/千克)得以恢复。我们的结果证实,青春期间歇性给予乙醇会诱导在成年期表现出来的长期影响,并且这些影响与寻求新奇表型之间存在关联。