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

Abstract

BackgroundForced 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.MethodsMale 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.ResultsWe 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 made more initiation omissions and were slower to initiate trials than H2O drinking controls, particularly during pretraining. EtOH drinking females were most affected. 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 discrimination and reversal phases, performance improved over time. We also observed sex-independent drinking group differences in win-stay and lose-shift strategies specific to the reversal phase.ConclusionsFemales exhibit increased vulnerability to EtOH effects in early learning: there were sex-dependent EtOH effects on attentional measures during pretraining and discrimination phases. We also found sexindependent EtOH effects on exploration strategies during reversal. Future studies should aim to uncover the neural mechanisms for changes in attention and exploration in both acute and prolonged EtOH withdrawal.

Theta oscillations in anterior cingulate cortex and orbitofrontal cortex differentially modulate accuracy and speed in flexible reward learning

“…After one week of post-surgery recovery, rats began the stimulus-based discrimination learning task (Figure 1B). This task was described in detail previously (Aguirre et al, 2020;Harris et al, 2020), however, in the present design we assigned deterministic stimulus-reward assignments -correct (100%) vs incorrect (0%). Rats initiated each trial by nosepoking a white graphic stimulus in the center screen (displayed for 40 s).…”

“…A causal investigation of their interaction in stimulus-based and actionbased learning in rodents is lacking in the broader literature. Further, we recently suggested that a thorough consideration of both accuracy and speed of response during learning may be particularly informative when identifying neural signatures of flexible learning (Aguirre et al, 2020;Harris et al, 2020).…”

Behavioral domains in compulsive rats: implications for understanding compulsive spectrum disorders

“…Compulsive HD animals exhibited decreased sensitivity to positive feedback compared with LD animals, showing decreased conditional win-stay probability (i.e., the probability of pressing the same lever rewarded in the previous trial). The insensitivity to reward contingencies has also been shown in different preclinical models of compulsive-like behavior: first, compulsive HD rats selected by SIP exhibited insensitivity to reinforcer devaluation and excessive habit formation measured by similar lever pressing under extinction after the consumption of either a different reinforcer or the same reinforcer compared with LD rats (Merchán et al, 2019); second, the rats exposed to chronic intermittent voluntary alcohol consumption, a model of alcohol use disorder, used win-stay strategy less than H 2 Odrinking rats (Aguirre et al, 2020); third, the animals exposed to alternation of a standard chow with a high palatable diet, a model of compulsive eating behavior, showed reduced sensitivity to d-amphetamine, suggestive of a hypofunctional reward system (Moore et al, 2020); and fourth, transgenic SAPAP3 −/− mice showed lower response rates and fewer attempts to collect food pellets in schedules of reinforcement tasks than wild-type mice, indicating altered reward processing (Ehmer et al, 2020). Finally, mirtazapine, an antidepressant with specific serotonergic effects, significantly increased the sensitivity to positive feedback, increasing the proportion of the win-stay strategy on the PSRL (Drozd et al, 2019).…”