Nicotine enhances the reinforcement of non-drug rewards by increasing nucleus accumbens (NAcc) reactivity to anticipatory cues. This anticipatory effect is selective as no clear evidence has emerged showing that nicotine acutely changes reward receipt reactivity. However, repeated rewarding experiences shift peak brain reactivity from hedonic reward outcome to the motivational anticipatory cue yielding more habitual cue-induced behavior. Given nicotine's influence on NAcc reactivity and connectivity, it is plausible that nicotine acutely induces this shift and alters NAcc functional connectivity during reward processing. To evaluate this currently untested hypothesis, a randomized crossover design was used in which healthy non-smokers were administered placebo and nicotine (2-mg lozenge). Brain activation to monetary reward anticipation and outcome was evaluated with functional magnetic resonance imaging. Relative to placebo, nicotine induced more NAcc reactivity to reward anticipation. Greater NAcc activation during anticipation was significantly associated with lower NAcc activation to outcome. During outcome, nicotine reduced NAcc functional connectivity with cortical regions including the anterior cingulate cortex, orbitofrontal cortex, and insula. These regions showed the same negative relationship between reward anticipation and outcome as noted in the NAcc. The current findings significantly improve our understanding of how nicotine changes corticostriatal circuit function and communication during distinct phases of reward processing and critically show that these alterations happen acutely following a single dose. The implications of this work explain nicotinic modulation of general reward function, which offer insights into the initial drive to smoke and the subsequent difficulty in cessation.

中文翻译：

---

尼古丁对奖励处理不同阶段的皮质纹状体反应的急性影响。

尼古丁通过增加伏隔核 (NAcc) 对预期线索的反应性来增强非药物奖励的强化。这种预期效应是选择性的，因为没有明确的证据表明尼古丁会急剧改变奖励收据反应性。然而，重复的奖励经历将大脑反应的峰值从享乐奖励结果转变为产生更多习惯性线索诱导行为的动机预期线索。鉴于尼古丁对 NAcc 反应性和连接性的影响，尼古丁在奖励处理过程中剧烈诱导这种转变并改变 NAcc 功能连接性是合理的。为了评估这个目前未经检验的假设，使用了随机交叉设计，其中健康的非吸烟者服用安慰剂和尼古丁（2 毫克锭剂）。用功能性磁共振成像评估大脑对金钱奖励预期和结果的激活。相对于安慰剂，尼古丁诱导更多的 NAcc 反应来奖励预期。预期期间较大的 NAcc 激活与较低的 NAcc 激活显着相关。结果期间，尼古丁降低了 NAcc 与皮质区域的功能连接，包括前扣带皮层、眶额皮质和岛叶。这些区域在奖励预期和结果之间表现出相同的负相关关系，如 NAcc 中所述。目前的研究结果显着提高了我们对尼古丁如何在奖励处理的不同阶段改变皮质纹状体回路功能和交流的理解，并批判性地表明，这些改变在单次剂量后迅速发生。