Ledesma Juan Carlos, Aguilar Maria A, Giménez-Gómez Pablo, Miñarro José, Rodríguez-Arias Marta
Departament de Psicobiologia, Universitat de València, Avda. Blasco Ibáñez 21, Valencia, Spain.
PLoS One. 2017 Mar 14;12(3):e0172956. doi: 10.1371/journal.pone.0172956. eCollection 2017.
Ethanol (EtOH) binge drinking is an increasingly common behavior among teenagers that induces long-lasting neurobehavioral alterations in adulthood. An early history of EtOH abuse during adolescence is highly correlated with cocaine addiction in adulthood. Abstinence of cocaine abuse can cause psychiatric symptoms, such as anxiety, psychosis, depression, and cognitive impairments. This study assessed the consequences of adolescent exposure to EtOH on the behavioral alterations promoted by cocaine withdrawal in adulthood.
We pretreated juvenile (34-47 days old) or adult (68-81 days old) mice with EtOH (1.25 g/kg) following a binge-drinking pattern. Then, after a three-week period without drug delivery, they were subjected to a chronic cocaine treatment in adulthood and tested under cocaine withdrawal by the ensuing paradigms: open field, elevated plus maze, prepulse inhibition, tail suspension test, and object recognition. Another set of mice were treated with the same EtOH binge-drinking procedure during adolescence and were tested immediately afterwards under the same behavioral paradigms.
Adolescent EtOH pretreatment undermined the anxiogenic effects observed after cocaine abstinence, reduced prepulse inhibition, and increased immobility scores in the tail suspension test following cocaine withdrawal. Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence. EtOH binge drinking during adolescence also induced anxiety, depressive symptoms, and memory impairments when measured immediately afterwards. In contrast, neither EtOH nor cocaine alone or in combination altered any of these behaviors when given in adulthood.
EtOH binge drinking induces short- and long-term behavioral alterations and modulates cocaine withdrawal symptoms when given in adolescent mice.
乙醇（EtOH）暴饮是青少年中日益常见的行为，会在成年期引发持久的神经行为改变。青少年时期早期的乙醇滥用史与成年期可卡因成瘾高度相关。戒除可卡因滥用会导致精神症状，如焦虑、精神病、抑郁和认知障碍。本研究评估了青少年接触乙醇对成年期可卡因戒断所促进的行为改变的影响。
我们按照暴饮模式用乙醇（1.25 g/kg）对幼年（34 - 47日龄）或成年（68 - 81日龄）小鼠进行预处理。然后，在停药三周后，它们在成年期接受慢性可卡因治疗，并通过以下范式在可卡因戒断状态下进行测试：旷场试验、高架十字迷宫试验、前脉冲抑制试验、悬尾试验和物体识别试验。另一组小鼠在青少年期接受相同的乙醇暴饮程序治疗，并在之后立即按照相同的行为范式进行测试。
青少年期乙醇预处理削弱了可卡因戒断后观察到的致焦虑作用，降低了前脉冲抑制，并增加了可卡因戒断后悬尾试验中的不动时间得分。此外，在青少年期接触乙醇的可卡因戒断小鼠中，这些物质单独使用时引起的记忆缺陷有所增强。青少年期乙醇暴饮之后立即测量还会诱发焦虑、抑郁症状和记忆障碍。相比之下，成年期单独给予乙醇或可卡因，或两者联合使用，均未改变任何这些行为。
在青少年小鼠中给予乙醇暴饮会诱发短期和长期的行为改变，并调节可卡因戒断症状。
