HIV Transgenic Rats Demonstrate Superior Task Acquisition and Intact Reversal Learning in the Within-Session Probabilistic Reversal Learning Task

Abstract

The HIV transgenic (HIVtg) rat is a commonly used animal model of chronic HIV infection that exhibits a wide range of cognitive deficits. To date, relatively little work has been conducted on these rats' capacity for reversal learning, an assay of executive function and cognitive flexibility used in humans. The present study sought to determine the impact of HIV genotype on probabilistic reversal learning, effortful motivation, and spontaneous locomotion/exploration in rats. Male (n = 8) and female (n = 8) HIVtg rats and wildtype (WT) controls were utilized. Cognitive flexibility was assessed via the Probabilistic Reversal Learning Task (PRLT), which reinforced responses to two stimuli on differential probabilistic schedules that periodically reversed. Effortful motivation and locomotor/exploratory behavior were assessed via the Progressive Ratio Breakpoint Task (PRBT) and the Behavioral Pattern Monitor (BPM), respectively. Regardless of sex, HIVtg rats required fewer trials to ascertain initial PRLT reward schedules than WT rats, and completed the same number of reversals. Secondary behaviors suggested that HIVtg PRLT performance was facilitated by a speed-accuracy tradeoff strategy. No main or interactive effects of genotype were observed in the PRBT or BPM. Relative to WT controls, HIVtg rats exhibited superior probabilistic reinforcement learning. Reversal learning was unaffected by HIV genotype, as was effortful motivation and exploratory behavior. These findings contrast with previous characterizations of the HIVtg rat, thus indicating a nuanced cognitive profile that is dependent upon such task specifications as within-versus between-session assessment and probabilistic versus deterministic reward schedules.

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“…In the BPM, females had increased motor activity, exploratory behavior, and more linear movement (lower spatial d ) compared to males. However, sex differences are not typically observed in BPM studies cross-species (Minassian et al, 2016; Risbrough et al, 2006; Roberts et al, 2021b). Contradictory to our current findings, one recent BPM study in mice found that males had increased motor activity, exploratory behavior, and more linear movement (Ayoub et al, 2023).…”

“…Such studies are important given the potential for human assessment of exploration in the BPM (Minassian et al, 2022;Young et al, 2007). A previous BPM study in HIV-1Tg rats reported no genotype differences, though these rats were previously operantly trained to perform probabilistic reversal learning task, which may have skewed genotype effects on motor activity, with smaller sample sizes (Roberts et al, 2021b). Furthermore, in the current study, rats were startled in PPI chambers prior to the BPM testing session, which may have had independent stress-induced effects on locomotor behavior.…”