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Noradrenergic modulation of risk/reward decision making

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Abstract

Rationale

Catecholamine transmission modulates numerous cognitive and reward-related processes that can subserve more complex functions such as cost/benefit decision making. Dopamine has been shown to play an integral role in decisions involving reward uncertainty, yet there is a paucity of research investigating the contributions of noradrenaline (NA) transmission to these functions.

Objectives

The present study was designed to elucidate the contribution of NA to risk/reward decision making in rats, assessed with a probabilistic discounting task.

Methods

We examined the effects of reducing noradrenergic transmission with the α2 agonist clonidine (10–100 μg/kg), and increasing activity at α2A receptor sites with the agonist guanfacine (0.1–1 mg/kg), the α2 antagonist yohimbine (1–3 mg/kg), and the noradrenaline transporter (NET) inhibitor atomoxetine (0.3–3 mg/kg) on probabilistic discounting. Rats chose between a small/certain reward and a larger/risky reward, wherein the probability of obtaining the larger reward either decreased (100–12.5 %) or increased (12.5–100 %) over a session.

Results

In well-trained rats, clonidine reduced risky choice by decreasing reward sensitivity, whereas guanfacine did not affect choice behavior. Yohimbine impaired adjustments in decision biases as reward probability changed within a session by altering negative feedback sensitivity. In a subset of rats that displayed prominent discounting of probabilistic rewards, the lowest dose of atomoxetine increased preference for the large/risky reward when this option had greater long-term utility.

Conclusions

These data highlight an important and previously uncharacterized role for noradrenergic transmission in mediating different aspects of risk/reward decision making and mediating reward and negative feedback sensitivity.

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Acknowledgments

This work was supported by a grant from the Canadian Institutes of Health Research (MOP 89861) to SBF. We thank Lauren Ogilvie for her assistance with behavioral testing. DRM and CMS contributed equally to this work.

Conflict of interest

The authors declare no conflicts of interest.

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Correspondence to Stan B. Floresco.

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Montes, D.R., Stopper, C.M. & Floresco, S.B. Noradrenergic modulation of risk/reward decision making. Psychopharmacology 232, 2681–2696 (2015). https://doi.org/10.1007/s00213-015-3904-3

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  • DOI: https://doi.org/10.1007/s00213-015-3904-3

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