Sex-dependent effects of chronic intermittent voluntary alcohol consumption on attentional, not motivational, measures during probabilistic learning and reversal

Abstract

Background Forced alcohol (ethanol, EtOH) exposure has been shown to cause significant impairments on reversal learning, a widely-used assay of cognitive flexibility, specifically on fully-predictive, deterministic versions of this task. However, previous studies have not adequately considered voluntary EtOH consumption and sex effects on probabilistic reversal learning. The present study aimed to fill this gap in the literature. Methods Male and female Long-Evans rats underwent either 10 weeks of voluntary intermittent 20% EtOH access or water only (H2O) access. Rats were then pretrained to initiate trials and learn stimulus-reward associations via touchscreen response, and subsequently required to select between two visual stimuli, rewarded with probability 0.70 or 0.30. In the final phase, reinforcement contingencies were reversed. Results We found significant sex differences on several EtOH-drinking variables, with females reaching a higher maximum EtOH consumption, exhibiting more high-drinking days, and escalating their EtOH at a quicker rate compared to males. During early abstinence, EtOH drinkers (and particularly EtOH-drinking females) made more initiation omissions and were slower to initiate trials than H2O drinking controls, especially during pretraining. A similar pattern in trial initiations was also observed in discrimination, but not in reversal learning. EtOH drinking rats were unaffected in their reward collection and stimulus response times, indicating intact motivation and motor responding. Although there were sex differences in

Unique features of stimulus-based probabilistic reversal learning

“…Finally, we found that differences in reward collection latencies depended on the richness of the environment (90% vs 70% reward). Notably, the only pronounced sex difference was in longer latencies to choose the better option during reversal learning (females taking longer than males), which is generally consistent with the pattern of effects of a recent study by our group (Aguirre et al, 2020). We elaborate on these findings below.…”

“…Further, we found that differences in reward collection latencies depended on the degree to which the environment was profitable (90% vs 70% reward). Finally, the only pronounced sex differences were uncovered for initiation latencies across both learning phases, and a greater number of initiation omissions during reversal learning, suggesting greater attentional demands in females relative to males, which replicate effects of a recent study by our group (Aguirre et al, 2020). We elaborate on these findings below.…”

“…Prior work utilized initiation omissions as measures of attentional deficits, and we found similar sex-specific effects for both initiation omissions and latencies. These effects were limited to specific phases, with females exhibiting more initiation omission during the discrimination learning phase, and longer initiation latencies during late reversal learning (Aguirre et al, 2020).…”

“…worse option). Consistent with prior literature showing freely-behaving rodents exhibit slow learning on probabilistic reversals with visual stimuli (Aguirre et al, 2020), most animals from either cohort did not meet a 70% criterion before the termination of the study, so we limited our analyses to the first seven sessions of discrimination and reveral phases for all animals.…”

Alcohol Consumption during Adulthood Does Not Impair Later Go/No-Go Reversal Learning in Male Rats

“…In some rodent models, prior alcohol exposure has impaired both the initial discrimination and the later reversal [9][10][11][12], whereas other experimental conditions found the original discrimination unimpaired and found a selective deficit in reversal learning [9,[13][14][15][16][17][18]. However, many studies have instead found that prior alcohol exposure does not lead to a discrimination or a reversal learning impairment [19][20][21][22][23][24][25]. The prior literature on the long-term effects of alcohol exposure on reversal learning spans procedures from multiple laboratories, which differ in multiple experimental factors (e.g., type of reversal learning task, method and dose of alcohol exposure, age of alcohol exposure, alcohol-test interval), and does not fit a consistent pattern in which a single factor can explain all of the conflicting results.…”