Abstract
Rationale
Risky choice can be measured using the risky decision task (RDT). In the RDT, animals choose between a large, risky option that is paired with probabilistic foot shock and a small, safe option that is never paired with shock. To date, studies examining the neurochemical basis of decision-making in the RDT have focused primarily on the dopaminergic system but have not focused on the glutamatergic system, which has been implicated in risky decision-making.
Objectives
Because glutamate is known to play a critical role in decision-making, we wanted to determine the contribution of the glutamatergic system to performance in the RDT.
Methods
In the experiment, 32 rats (16 male; 16 female) were tested in the RDT. The probability of receiving a foot shock increased across the session (ascending schedule) for half of the rats but decreased across the session (descending schedule) for half of the rats. Following training, rats received injections of the N-methyl-d-aspartate (NMDA) receptor competitive antagonist CGS 19755 (0, 1.0, 2.5, 5.0 mg/kg; s.c.) and the GluN2B-selective antagonist Ro 63-1908 (0, 0.1, 0.3, 1.0 mg/kg; s.c.).
Results
CGS 19755 (2.5 and 5.0 mg/kg) increased risky choice in males and females trained on the ascending schedule. Ro 63-1908 (1.0 mg/kg) decreased risky choice, but only in male rats trained on the ascending schedule.
Conclusions
Although NMDA receptor antagonists differentially alter risky choice in the RDT, the current results show that NMDA receptors are an important mediator of decision-making involving probabilistic delivery of positive punishment.
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Notes
In traditional discounting functions, A simply refers to reinforcer amount (typically the amount of the large magnitude reinforcer). This definition can be problematic in animal behavioral pharmacology experiments, in which pharmacological manipulations can drastically alter an animal’s preference for the large magnitude reinforcer, even when its delivery is immediate/guaranteed/delivered without shock.
There were 26 rats that received all eight injections (208 injections), two rats that received 10 injections (due to retraining that occurred after receiving the second injection during the second set of injections; 20 injections), one rat that received three injections before losing stimulus control, and one rat that received one injection before losing stimulus control.
Because we used the percentage of receiving foot shock for the x-axis as opposed to the odds against receiving no shock, the proportion of responses for the large, risky option appears to decrease linearly as a function of probability. If we express the x-axis as odds against, the data are curvilinear, thus making the use of an exponential function appropriate.
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Acknowledgments
We would like to thank the NIMH Chemical Synthesis and Drug Supply Program for generously providing the CGS 19755 used in the current experiment. We would also like to thank Karson Evans and Kadyn Lilly for the technical assistance during the pilot studies that were important for the development of the current study.
Funding
The current study was supported by NIH grant R15DA047610 and NIGMS grant P20GM103436. The study was also supported by a Northern Kentucky University Faculty Project Grant and a Northern Kentucky University College of Arts and Sciences Professional Development Award.
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Yates, J.R., Horchar, M.J., Ellis, A.L. et al. Differential effects of glutamate N-methyl-d-aspartate receptor antagonists on risky choice as assessed in the risky decision task. Psychopharmacology 238, 133–148 (2021). https://doi.org/10.1007/s00213-020-05664-z
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DOI: https://doi.org/10.1007/s00213-020-05664-z