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.

Adolescent chronic sleep restriction promotes alcohol drinking in adulthood: evidence from epidemiological and preclinical data

“…If anything, relative to controls, CSR rats showed a tendency towards a less anxious-like behavior in the open field test and in the NSF test. At first glance, these results could appear counterintuitive because existent reports showed that repeated adolescent alcohol binge drinking [75] and sleep loss [76] can increase anxiety and depressive symptoms in early and mid- adulthood. On the other hand, it is also known that disrupted sleep is associated with global risky decision making in adolescents, including illicit substance use, sexual risk-taking, and road/transport-related safety [10].…”

Aerobic Physical Training Attenuates Oxidative Stress in the Spinal Cord of Adult Rats Induced by Binge-like Ethanol Intake

“…The animals were weekly weighted to adjust the dose. The binge-like EtOH administrations aimed to simulate a pattern of compulsive consumption for 4 weeks [22,24,43].…”