Abstract
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.
Highlights
Many reports indicate that alcohol is one of the first drugs of choice among young people and adolescents and that heavy bingedrinking is increasingly frequent among this age group in numerous countries [1,2,3]
Our results confirm that EtOH binge drinking during adolescence induces long-lasting effects that continue to manifest themselves in adult life
Regardless of novelty phenotype, exposure during adolescence to a binge pattern of EtOH administration produced an increase in the reinforcing effects of cocaine and MDMA, as they developed CPP with a sub-threshold dose of these drugs
Summary
Many reports indicate that alcohol is one of the first drugs of choice among young people and adolescents and that heavy bingedrinking is increasingly frequent among this age group in numerous countries [1,2,3]. Concerns about heavy drinking during adolescence - a period of brain maturation - have grown since recent evidence demonstrated that it can have a negative impact on brain structure and function, causing significant short- and long-term cognitive and behavioral consequences [7]. These damaging effects of EtOH are usually irreversible [8]. Studies in rodents have shown that adolescent animals are less sensitive to the negative consequences of alcohol on motor impairment [14] or in terms of hangover effects [15], but are more sensitive than adults to some of its pleasurable effects, including social facilitation [16]
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