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Pharmacological evidence that 5-HT2C receptor blockade selectively improves decision making when rewards are paired with audiovisual cues in a rat gambling task

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Abstract

Rationale

Adding reward-concurrent cues to a rat gambling task (rGT) increases risky choice. This cued version of the task may reflect an “addiction-like” cognitive process, more similar to human gambling than the uncued task. Serotonergic drugs that target 5-HT2 receptors alter mechanisms linked to impulse control. However, relatively little is known regarding the impact of such agents on either risky decision making, or the ability of conditioned stimuli to bias the choice process, despite potential relevance to addiction development and treatment.

Objectives

The aim of this study was to determine the effects of SB 242,084 and M100907, selective antagonists at the 5-HT2C and 5-HT2A receptors respectively, as well as the selective 5-HT2C receptor agonist Ro-60-0175, on performance of both cued and uncued versions of the rGT.

Results

SB 242,084 significantly and dose-dependently increased choice of the most optimal option in the cued rGT only, despite concurrently increasing impulsive responses made prematurely on both the cued and uncued rGT. M100907 and Ro-60-0175 did not alter risky decision making, but nevertheless produced the expected decrease in premature responses on both task variants.

Conclusions

These findings demonstrate that the 5-HT2 receptor-mediated regulation of risky decision making and motor impulsivity can be pharmacologically dissociated and further show that the presence of highly salient reward-paired cues critically alters the neurochemical regulation of the choice process. Importantly, these results suggest that 5-HT2C receptor antagonists may be of use in disrupting maladaptive patterns of decision making.

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Acknowledgements

This work was supported in part by a Medical Research Council grant (DPFS grant, MR/L013150/1). CAW also received salary support through the Canadian Institutes for Health Research (CIHR) New Investigator Award program. WA was supported by philanthropic funding provided by Paul and Diane Erickson and the Gillespie family. Over the past 3 years, CAW has consulted for Shire and Hogan Lovells LLP and received due compensation.

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  1. Wendy K. Adams, Chris Barkus and Jacqueline-Marie N. Ferland contributed equally.

Authors and Affiliations

  1. Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada

    Wendy K. Adams, Chris Barkus, Jacqueline-Marie N. Ferland & Catharine A. Winstanley

  2. Department of Pharmacology, University of Oxford, Oxford, UK

    Chris Barkus & Trevor Sharp

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  1. Wendy K. Adams
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Correspondence to Catharine A. Winstanley.

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Adams, W.K., Barkus, C., Ferland, JM.N. et al. Pharmacological evidence that 5-HT2C receptor blockade selectively improves decision making when rewards are paired with audiovisual cues in a rat gambling task. Psychopharmacology 234, 3091–3104 (2017). https://doi.org/10.1007/s00213-017-4696-4

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