Montes David R, Stopper Colin M, Floresco Stan B
Department of Psychology and Brain Research Centre, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Psychopharmacology (Berl). 2015 Aug;232(15):2681-96. doi: 10.1007/s00213-015-3904-3. Epub 2015 Mar 13.
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 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.
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.
儿茶酚胺传递调节众多认知和奖赏相关过程，这些过程可支持更复杂的功能，如成本/收益决策。多巴胺已被证明在涉及奖赏不确定性的决策中起不可或缺的作用，但关于去甲肾上腺素（NA）传递对这些功能的贡献的研究却很少。
本研究旨在阐明NA对大鼠风险/奖赏决策的贡献，采用概率折扣任务进行评估。
我们研究了用α2激动剂可乐定（10 - 100μg/kg）降低去甲肾上腺素能传递，以及用激动剂胍法辛（0.1 - 1mg/kg）、α2拮抗剂育亨宾（1 - 3mg/kg）和去甲肾上腺素转运体（NET）抑制剂托莫西汀（0.3 - 3mg/kg）增加α2A受体位点活性对概率折扣的影响。大鼠在小/确定奖赏和大/风险奖赏之间进行选择，其中获得大奖赏的概率在一个实验过程中要么降低（100% - 12.5%）要么增加（12.5% - 100%）。
在训练良好的大鼠中，可乐定通过降低奖赏敏感性减少了风险选择，而胍法辛不影响选择行为。育亨宾通过改变负反馈敏感性，在一个实验过程中随着奖赏概率的变化损害了决策偏差的调整。在一部分对概率奖赏表现出显著折扣的大鼠中，当大/风险奖赏选项具有更大的长期效用时，最低剂量的托莫西汀增加了对该选项的偏好。
这些数据突出了去甲肾上腺素能传递在介导风险/奖赏决策的不同方面以及介导奖赏和负反馈敏感性方面的重要且先前未被描述的作用。
