Repeated Cycles of Binge-Like Ethanol Exposure Induces Neurobehavioral Changes During Short- and Long-Term Withdrawal in Adolescent Female Rats

Abstract

Alcohol consumption is spread worldwide and can lead to an abuse profile associated with severe health problems. Adolescents are more susceptible to addiction and usually consume ethanol in a binge drinking pattern. This form of consumption can lead to cognitive and emotional disorders, however scarce studies have focused on long-term hazardous effects following withdrawal periods after binge drinking in adolescents. Thus, the present study aims at investigating whether behavioral and cognitive changes persist until mid and late adulthood. Female Wistar rats (9-10 animals/group) received intragastric administration of four cycles of ethanol binge-like pattern (3.0 g/kg/day, 20% w/v; 3 days-on/4 days-off) from 35th to 58th days old, followed withdrawal checkpoints 1 day, 30 days, and 60 days. At each checkpoint period, behavioral tests of open field, object recognition test, elevated plus maze, and forced swimming test were performed, and blood and hippocampus were collected for oxidative biochemistry and brain-derived neurotrophic factor (BDNF) levels analysis, respectively. The results demonstrated that adolescent rats exposed to binge drinking displayed anxiogenic- and depressive-like phenotype in early and midadulthood, however, anxiety-like profile persisted until late adulthood. Similarly, short-term memory was impaired in all withdrawal periods analysed, including late adult life. These behavioral data were associated with oxidative damage in midadulthood but not BDNF alterations. Taken together, the present work highlights the long-lasting emotional and cognitive alterations induced by ethanol binge drinking during adolescence, even after a long period of abstinence, which might impact adult life.