Serotonin is widely implicated as a modulator of brain reward function. However, laboratory studies have not yielded a consensus on which specific reward-related processes are influenced by serotonin and in what manner. Here we explored the role of serotonin in cue-reward learning in mice. In a first series of experiments, we found that acute administration of the serotonin reuptake inhibitors citalopram, fluoxetine, or duloxetine all reduced lever pressing reinforced on an FR1 schedule with presentation of a cue that had been previously paired with delivery of food. However, citalopram had no effect on responding that was reinforced with both cue and food on an FR1 schedule. Furthermore, citalopram did not affect nose poke responses that produced no auditory, visual, or proprioceptive cues but were reinforced with food pellets on a progressive ratio schedule. We next performed region-specific knock out of tryptophan hydroxylase-2 (Tph2), the rate-limiting enzyme in serotonin synthesis. Viral delivery of Cre recombinase was targeted to dorsal or median raphe nuclei (DRN, MRN), the major sources of ascending serotonergic projections. MRN but not DRN knockouts were impaired in development of cue-elicited approach during Pavlovian conditioning; both groups were subsequently hyper-responsive when lever pressing for cue presentation. The inhibitory effect of citalopram was attenuated in DRN but not MRN knockouts. Our findings are in agreement with prior studies showing serotonin to suppress responding for conditioned reinforcers. Furthermore, these results suggest an inhibitory role of MRN serotonin neurons in the initial attribution of motivational properties to a reward-predictive cue, but not in its subsequent maintenance. In contrast, the DRN appears to promote the reduction of motivational value attached to a cue when it is presented repeatedly in the absence of primary reward.

血清素被广泛认为是大脑奖赏功能的调节剂。然而，实验室研究尚未就哪些特定的奖励相关过程受血清素影响以及以何种方式影响达成共识。在这里，我们探讨了血清素在小鼠提示奖励学习中的作用。在第一系列实验中，我们发现，急性给予 5-羟色胺再摄取抑制剂西酞普兰、氟西汀或度洛西汀都可以减少 FR1 计划中加强的杠杆压力，并呈现先前与食物递送配对的提示。然而，西酞普兰对 FR1 计划中的提示和食物强化的反应没有影响。此外，西酞普兰不影响不产生听觉、视觉、或本体感受线索，但在渐进比例计划中用食物颗粒加强。我们接下来对色氨酸羟化酶 2 进行了区域特异性敲除（Tph2)，血清素合成中的限速酶。Cre重组酶的病毒递送靶向背侧或中缝核（DRN，MRN），这是5-羟色胺能上升投射的主要来源。在巴甫洛夫条件反射期间，MRN 而不是 DRN 敲除在线索引发方法的发展中受损；随后，当杠杆按下提示呈现时，两组都反应过度。西酞普兰的抑制作用在 DRN 中减弱，但在 MRN 敲除中没有减弱。我们的研究结果与先前的研究一致，这些研究表明血清素可以抑制对条件强化物的反应。此外，这些结果表明 MRN 血清素神经元在最初将动机特性归因于奖励预测线索中具有抑制作用，但在其随后的维持中没有抑制作用。相比之下，