Alcohol or stress exposure during late adolescence impairs risk assessment later in life, disrupting the ethological structure of behavior in mice

Abstract Background Decision-making is a key component of adaptive behavior and relies on risk assessment as a critical process that enables organisms to evaluate threats before exploring potentially dangerous areas. During adolescence, this process is particularly vulnerable to disruption by external factors such as stress and substance use, potentially leading to changes in the structure of defensive and exploratory behaviors, potentially leading to riskier choices. Methods We investigated whether repeated ethanol intoxication or pharmacological stress during late adolescence (7-8 weeks of age) alters overall behavioral structure, focusing on risk assessment behaviors, in adulthood. Male and female C57BL/6 mice received four intermittent injections of saline, ethanol (4.0 g/kg), or the α2-adrenergic antagonist yohimbine (2.0 mg/kg). In early adulthood (9th week), animals were tested in the Light–Dark Box and Elevated Plus Maze. In addition to traditional anxiety-like behavior and exploratory measures, risk assessment behaviors (stretches and head outs) were classified as NoGo (risk evaluation without entering the aversive area) or Go (risk evaluation followed by exploration), and behavioral organization was examined using first-order Markov chain analyses. Results Both ethanol and yohimbine exposure produced persistent reductions in NoGo risk assessment behaviors in adulthood, in both sexes, with minimal effects on classical anxiety-like measures. Correlation and transition probability analyses revealed a reorganization of behavioral structure, characterized by reduced transitions toward risk assessment events and a bias toward risk-taking actions. Conclusions These findings indicate that repeated late adolescent alcohol intoxication and stress exposure induce long-lasting alterations in risk assessment and decision-making strategies.