Researchers employed a novel dynamic probabilistic reversal learning (dynaPRL) task to investigate the impact of chronic ethanol (EtOH) dependence in rats, particularly the striatal encoding of reward learning signals.
The study revealed that EtOH induces significant alterations in exploration-exploitation trade-offs and several other behavioral metrics, with distinct neural adaptations in females and impairments predominantly in male rats. These behavioral deficits were long-term, persisting for more than 10 weeks after the last EtOH exposure.
These findings highlight that female and male rats differ in their neural encoding patterns and provide novel insights into the sex-specific effects of EtOH dependence in decision-making.
Study
The present study aims to address current knowledge deficits by leveraging novel dynamic probabilistic reversal learning (dynaPRL) tasks on male and female rats. The rats used in these experiments were 10-week-old wild-type Long-Evans (LE) rats (male n = 17, female n = 10).
Behavioral experiments were carried out in several sequential phases. All experiments were conducted in a custom-designed, soundproof modular operant chamber, which included a reward magazine fitted with two levers. Rodent entry into the reward magazine triggered lever insertion.
Pressing a lever resulted in rats being presented either with a reward (100-μl sucrose solution) or no reward. During the first (training) phase, pressing either lever resulted in reward delivery with a 100% probability. During the second (reversal task training) phase, only one lever provided the reward, while pressing the other gave no reward.
The standard probabilistic reversal learning (PRL) task experiment was carried out between one and three days following the above learning phase. The experiment consisted of pressing the correct lever, resulting in reward delivery 70% of the time. If the wrong lever was pressed, there was a 10% chance of the ‘reward’ lever becoming the ‘no reward’ lever and vice versa. Based on their performance in the PRL task, rats were separated into EtOH-exposed (male n = 8, female n = 5) and control (air; male n = 9, female n = 5) cohorts.
Exposure to either EtOH vapor or air was carried out for 14 hours, followed by 10 hours of withdrawal, with the procedure repeated over five consecutive days. Blood was routinely extracted from rodent tails to measure their blood EtOH concentrations (BECs). Several behavioral metrics (e.g., reversal performance) were used to record rodent behavior events during both the PRL and dynaPRL experiments.
Rats were further surgically implanted with custom-made electrode arrays to record their neural signals during behavioral experiments.
The novel dynaPRL task maintained the same average reward probability as the standard PRL task experiment but introduced unpredictable block transitions: The probability of pressing the correct lever delivering a reward and the likelihood of a block transition were assigned to a pseudorandomly chosen block. Each block had its own paired probabilities: 1. 45% reward, 45% lever swap, 2. 60% reward, 30% lever swap, 3. 80% reward, 10% lever swap.
These blocks varied in expected and unexpected uncertainty, as suggested by the authors, requiring rats to flexibly adapt their behavior to shifting reward contingencies. “The lever outcome contingencies were randomly reversed to one of the three blocks every 15 to 30 trials, except when a rat made four or more consecutive incorrect choices within certain trial blocks.”
Results
The present study produces several notable findings: Withdrawal from chronic EtOH exposure did not appreciably alter individual-specific performance in the standard PRL task. No differences were observed between male and female rats for either EtOH-exposed or controls.
The dynaPRL task, however, proved substantially more cognitively challenging for EtOH-exposed rats, with marked performance deficits noted compared to controls. While controls could adapt their standard PRL training to the dynaPRL task, EtOH-exposed rats (especially males) found difficulties doing so. Notably, female EtOH-exposed rats showed minimal behavioral deficits over time, while male performance did not improve even after 10 weeks of abstinence.
Support vector machine (SVM) analyses confirmed these findings, further revealing that male EtOH-exposed rats suffered from slowed adaptive learning, reduced exploration, and altered outcome-specific value updating, all of which affected their behavioral outcomes (obtaining the reward). SVM decoding was significant in males only; females were not classifiable by treatment group.
Neural recordings showed that male rats had reduced choice-related signaling in the DMS but heightened outcome encoding, whereas females exhibited distinct neural adaptations without corresponding behavioral deficits.
Conclusion
The present study sheds light on the mechanisms underpinning value computation impairments in chronic EtOH-exposed rats. It highlights their sex-dependent effects (male performance impaired more strongly than female) and protracted effects in males, suggesting distinct sex-specific neural dynamics in value-based decision processing.
Source:
https://www.news-medical.net/news/20250410/Alcohol-reshapes-reward-learning-differently-in-male-and-female-rats.aspx