Noradrenergic modulation of risk/reward decision making

被引:36
作者
Montes, David R. [1 ,2 ]
Stopper, Colin M. [1 ,2 ]
Floresco, Stan B. [1 ,2 ]
机构
[1] Univ British Columbia, Dept Psychol, Vancouver, BC V6T 1Z4, Canada
[2] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 1Z4, Canada
基金
加拿大健康研究院;
关键词
Decision making; Noradrenaline; Risk; Probabilistic discounting; alpha; 2; Receptors; Rat; SPATIAL WORKING-MEMORY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; CLONIDINE-INDUCED SEDATION; MEDIAL PREFRONTAL CORTEX; DOPAMINE D-1 RECEPTORS; RAT GAMBLING TASK; CATECHOLAMINE RECEPTORS; ORBITOFRONTAL CORTEX; AGONIST CLONIDINE;
D O I
10.1007/s00213-015-3904-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. The present study was designed to elucidate the contribution of NA to risk/reward decision making in rats, assessed with a probabilistic discounting task. We examined the effects of reducing noradrenergic transmission with the alpha 2 agonist clonidine (10-100 mu g/kg), and increasing activity at alpha 2A receptor sites with the agonist guanfacine (0.1-1 mg/kg), the alpha 2 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. 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. 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.
引用
收藏
页码:2681 / 2696
页数:16
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