University of Colorado Denver, Denver, CO 80217.
eNeuro. 2018 May 15;5(2). doi: 10.1523/ENEURO.0058-18.2018. eCollection 2018 Mar-Apr.
While an extensive literature supports the notion that mesocorticolimbic dopamine plays a role in negative reinforcement, recent evidence suggests that dopamine exclusively encodes the value of positive reinforcement. In the present study, we employed a behavioral economics approach to investigate whether dopamine plays a role in the valuation of negative reinforcement. Using rats as subjects, we first applied fast-scan cyclic voltammetry (FSCV) to determine that dopamine concentration decreases with the number of lever presses required to avoid electrical footshock (i.e., the economic price of avoidance). Analysis of the rate of decay of avoidance demand curves, which depict an inverse relationship between avoidance and increasing price, allows for inference of the worth an animal places on avoidance outcomes. Rapidly decaying demand curves indicate increased price sensitivity, or low worth placed on avoidance outcomes, while slow rates of decay indicate reduced price sensitivity, or greater worth placed on avoidance outcomes. We therefore used optogenetics to assess how inducing dopamine release causally modifies the demand to avoid electrical footshock in an economic setting. Increasing release at an avoidance predictive cue made animals more sensitive to price, consistent with a negative reward prediction error (i.e., the animal perceives they received a worse outcome than expected). Increasing release at avoidance made animals less sensitive to price, consistent with a positive reward prediction error (i.e., the animal perceives they received a better outcome than expected). These data demonstrate that transient dopamine release events represent the value of avoidance outcomes and can predictably modify the demand to avoid.
虽然大量文献支持中脑边缘多巴胺在负强化中起作用的观点，但最近的证据表明，多巴胺专门编码正强化的价值。在本研究中，我们采用行为经济学方法来研究多巴胺是否在负强化的评估中起作用。我们使用大鼠作为研究对象，首先应用快速扫描循环伏安法（FSCV）来确定多巴胺浓度随着避免电击所需的按压次数而降低（即避免的经济价格）。避免需求曲线衰减率的分析描绘了避免与增加价格之间的反比关系，从而可以推断出动物对避免结果的重视程度。避免需求曲线迅速衰减表明对价格的敏感性增加，或者对避免结果的重视程度降低，而缓慢的衰减率则表明对价格的敏感性降低，或者对避免结果的重视程度增加。因此，我们使用光遗传学来评估在经济环境中诱导多巴胺释放如何因果地改变对避免电击的需求。在避免预测线索时增加释放会使动物对价格更加敏感，这与负奖励预测误差一致（即动物认为他们的结果比预期的更差）。在避免时增加释放会使动物对价格的敏感性降低，这与正奖励预测误差一致（即动物认为他们的结果比预期的更好）。这些数据表明，短暂的多巴胺释放事件代表了避免结果的价值，并可以预测性地改变对避免的需求。
