Adolescent but not adult ethanol binge drinking modulates cocaine withdrawal symptoms in mice

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 Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence.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.

Adolescent binge‐ethanol accelerates cognitive impairment and β‐amyloid production and dysregulates endocannabinoid signaling in the hippocampus of APP/PSE mice

“…7,8 Other studies demonstrate that chronic EtOH is more harmful, inducing greater long-term cognitive impairments when administered in adolescent animals than when this treatment is given in the adulthood. [9][10][11] Therefore, all this research confirms that both the way and the age of EtOH consumption is especially critical for the deleterious effects in adult and elderly cognitive performance.…”

Differential Impact of Ad Libitum or Intermittent High-Fat Diets on Bingeing Ethanol-Mediated Behaviors

“…Conversely, we observed that, independently of HFD consumption, mice exposed to EtOH presented deep disturbances on memory retrieval and learning, in line with previous reports showing that chronic and intermittent EtOH administration during adolescence decreases memory performance in the object recognition test [35,60,61]. Surprisingly, HFD (both ad libitum and binge) mitigated the effect of EtOH on the DI in the object recognition test, suggesting that HFD has a protective effect, which could be linked to an interference with EtOH pharmacokinetics, although this circumstance was not observed in a recent study carried out in our laboratory [16].…”

“…The present study evaluates, for the first time, the behavioral profile of adult animals that have been exposed during adolescence to EtOH binge drinking combined with an HFD. Taking into account previous studies modeling binge-drinking behavior [34,35], intermittent EtOH administration was administered to adolescent mice that had been exposed to either a standard diet (SD), continuous access to an HFD (ad libitum HFD), or limited and intermittent access to an HFD (Binge HFD). We sought to establish an eventual correlation between behavioral impairment and biochemical parameters associated with energy metabolism.…”

Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice

“…Further research is needed to determine the long-lasting effects of cannabis and its derivatives on anxiety. With respect to the effects of cocaine abstinence, we demonstrated that cessation of cocaine administration in adult mice treated with saline during adolescence evoked anxiety-like behaviors, in agreement with earlier studies in rats [41,62,63,64,65,66] and mice [55]. However, a very interesting result of the present study is that the anxiety values displayed by the animals pre-treated with WIN and later with cocaine did not differ from those of control mice.…”

“…This incongruity could be explained by a ceiling effect on the disruption of PPI induced by WIN exposure. In an earlier study, we demonstrated that exposure to an EtOH binge-drinking procedure during adolescence, which is not able to alter the PPI by itself, impairs the startle reflex in mice exposed to the same cocaine withdrawal as that of the current study [55]. This supports the notion that previous drug exposure during the adolescent period may enhance the putative psychotic-like actions of cocaine in mice.…”