Effect of Adolescent Alcohol Use on Encoding of Decision-Related Variables in Prefrontal Cortex

Adolescence is a critical period for neural development of the Prefrontal Cortex (PFC), an area that is implicated in encoding reward value and driving decision-making behavior. The continuing maturation of PFC during adolescence makes it susceptible to alcohol induced alterations in anatomy and function, leading to behavioral deficits. Repeated exposure to alcohol during adolescence has been associated with long-term, disrupted reward processing, which may manifest as elevated risk-preference. To determine the neural mechanisms underlying this phenotype, neural activity in Orbitofrontal Cortex (OFC) and Medial Prefrontal Cortex (mPFC) was measured while male and female rats, who had been exposed to alcohol in adolescence, performed a probabilistic risk-task. Rats voluntarily consumed a 10% alcohol by weight gelatin medium at the onset of the dark cycle on an intermittent schedule throughout adolescence (PD31-50). In adulthood, rats had bilateral microelectrode arrays stereotaxically implanted into OFC and mPFC. Neural activity was recorded as they performed a probabilistic risk task in which preference for large-risky rewards compared with small-certain rewards was measured. Probability of large-risky reward delivery varied between sessions to assess changes in risk-preference across different reward conditions. Adolescent alcohol use had a negative effect on preference for the large-risky lever, indicating rats were no longer able to modulate behavior in response to the changing session parameters. Increased alcohol use was associated with indiscriminate OFC activity that failed to differentiate reward sizes. The inability to discriminate reward sizes through variable firing rates was due to the blunting of neural activity in males and an increase in activity in females. High alcohol consuming rats also had decreased mPFC activity before selecting the large-risky lever, mirroring the alcohol-induced changes in behavior. The results suggest that adolescent alcohol use inhibits OFC from properly signaling the value of rewards the result from a decision and mPFC influences the direction of the resulting behavioral deficits.