Reward maximization assessed using a sequential patch depletion task in a large sample of heterogeneous stock rats

Abstract

Choice behavior requires animals to evaluate both short- and long-term advantages and disadvantages of all potential alternatives. Impulsive choice is traditionally measured in laboratory tasks by utilizing delay discounting (DD), a paradigm that offers a choice between a smaller immediate reward, or a larger more delayed reward. This study tested a large sample of Heterogeneous Stock (HS) male (n = 896) and female (n = 898) rats, part of a larger genetic study, to investigate whether measures of reward maximization overlapped with traditional models of delay discounting via the patch depletion model using a Sequential Patch Depletion procedure. In this task, rats were offered a concurrent choice between two water “patches” and could elect to “stay” in the current patch or “leave” for an alternative patch. Staying in the current patch resulted in decreasing subsequent reward magnitudes, whereas the choice to leave a patch was followed by a delay and a resetting to the maximum reward magnitude. Based on the delay in a given session, different visit durations were necessary to obtain the maximum number of rewards. Visit duration may be analogous to an indifference point in traditional DD tasks. Males and females did not significantly differ on traditional measures of DD (e.g. delay gradient; AUC). When examining measures of patch utilization, females made fewer patch changes at all delays and spent more time in the patch before leaving for the alternative patch compared to males. Consistent with this, there was some evidence that females deviated from reward maximization more than males. However, when controlling for body weight, females had a higher normalized rate of reinforcement than males. Measures of reward maximization were only weakly associated with traditional DD measures and may represent distinctive underlying processes. Taken together, females performance differed from males with regard to reward maximization that were not observed utilizing traditional measures of DD, suggesting that the patch depletion model was more sensitive to modest sex differences when compared to traditional DD measures in a large sample of HS rats.

Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats

“…Here, each 3MB window surrounding a top SNP for each identified QTL was tested for its association with a separate set of behavioral traits collected at each of three HS rat testing centers (University at Buffalo, University of Michigan, University of Tennessee Health Science Center) (Table 4). These traits included socially acquired nicotine self-administration (Wang et al, 2018), cocaine contextual conditioning (Hughson et al, 2019;King et al, 2021), sequential patch depletion (Gancarz et al, 2023;Ishiwari et al, 2023), light reinforcement (Gancarz et al, 2012(Gancarz et al, , 2013Ishiwari et al, 2023), locomotor response to novelty, reaction time, and social reinforcement (Ishiwari et al, 2023). Table 4 shows key measures for each behavioral task, selected based on the relevance to the trait being measured (full list of PheWAS results for each task are available in Supplementary Materials) We found that loci associated with attribution of incentive salience overlapped with those associated with measures of drug response (Table 4a).…”

“…However, more complex behavior, including measures of foraging and impulse control, yielded PheWAS associations that varied widely by task and measure. For example, during a patch-depletion foraging test (Gancarz et al, 2023), water-deplete rats consume water in one of two "patches", in which the amount of water available at a particular patch depletes over time. Switching patches is therefore adaptive in response to patch depletion that varies between subjects (Richards et al, 2013), but patch switching results in one of several experimenter-imposed delays.…”