Abstract
BackgroundEthanol (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.MethodsWe 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.ResultsAdolescent 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 Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence.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.ConclusionsEtOH binge drinking induces short- and long-term behavioral alterations and modulates cocaine withdrawal symptoms when given in adolescent mice.
Highlights
Many studies indicate that ethyl alcohol is one of the first drugs of choice among young people, and that binge drinking is increasingly frequent among this age group in numerous countries [1,2,3]
Study 1: Long-term effects of adolescent EtOH binge drinking after cocaine withdrawal in adulthood on locomotor activity, elevated plus maze, prepulse inhibition, tail suspension, and object recognition
Study 1: Long-term effects of adolescent EtOH binge drinking after cocaine withdrawal in adulthood on elevated plus maze, prepulse inhibition, tail suspension, and object recognition
Summary
Many studies indicate that ethyl alcohol (ethanol, EtOH) is one of the first drugs of choice among young people, and that binge drinking is increasingly frequent among this age group in numerous countries [1,2,3]. It has been reported that early onset and higher frequency of EtOH consumption is a reliable predictor of later problematic abuse of other illicit drugs in adulthood [8,9] This is known as the “gateway hypothesis”, which states that a causal relationship exists between early exposure to drugs and the abuse of other substances later in life [10,11,12] In accordance with this theory, it has been demonstrated that addiction to cocaine, the most used illicit drug in developed countries after cannabinoids, is strongly correlated with an early history of EtOH abuse in adolescence [13,14,15]. Abuse of this substance and its subsequent withdrawal can cause psychiatric symptoms, among which anxiety, psychosis, and depression prevail, while it induces cognitive impairments [17,18,19,20,21]
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