Alcohol or Stress Exposure During Late Adolescence Impairs Risk Assessment Later in Life, Disrupting the Ethological...

Decision-making relies on risk assessment as a critical process that enables organisms to evaluate threats before exploring potentially dangerous areas. While adolescence is a period of heightened vulnerability to external factors such as substance use and stress, it remains unclear how these factors disrupt risk assessment, particularly at the level of behavior structure: sequential actions, organization and transition probabilities between defensive and exploratory behaviors. We investigated whether repeated ethanol intoxication or pharmacological stress during late adolescence alters behavioral structure in early 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) during late adolescence (7-8^th weeks). In early adulthood (9^th week), animals were tested in the Light-Dark Box and Elevated Plus Maze. In addition to measuring classical anxiety-like and exploratory behavior, we focused on risk assessment behaviors (stretches/head-outs) categorized as NoGo (evaluation without entering the aversive area) or Go (evaluation followed by entry). We used 1^st order transition probability Markov chain analyses to map the transitions between these states, defining the behavioral structure.

Both ethanol and yohimbine produced persistent reductions in NoGo risk assessment behaviors in adulthood, in both sexes, with minimal effects on classical anxiety-like and exploratory measures. Transition probability and correlation analyses revealed a reorganization of behavioral structure, characterized by reduced transitions toward risk assessment events and a bias toward risk-taking actions.

These findings indicate that repeated late adolescent alcohol intoxication or stress exposure induces long-lasting alterations in risk assessment and decision-making strategies.