PMID- 29221752 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20191210 IS - 1095-9572 (Electronic) IS - 1053-8119 (Linking) VI - 169 DP - 2018 Apr 1 TI - Chronic nicotine exposure impairs uncertainty modulation on reinforcement learning in anterior cingulate cortex and serotonin system. PG - 323-333 LID - S1053-8119(17)30993-X [pii] LID - 10.1016/j.neuroimage.2017.11.048 [doi] AB - Deficits in the computational processes of reinforcement learning have been suggested to underlie addiction. Additionally, environmental uncertainty, which is encoded in the anterior cingulate cortex (ACC), modulates reward prediction errors (RPEs) during reinforcement learning and exacerbates addiction. The present study tested whether and how the ACC would have an essential role in drug addiction by failing to use uncertainty to modulate the RPEs during reinforcement learning. In Experiment I, we found that the ACC/medial prefrontal cortex (MPFC) did not modulate RPE learning according to uncertainty in smokers. The effect of uncertainty x RPE in the ACC/MPFC was correlated with the learning rate of RPEs and the duration of nicotine use. Experiment II demonstrated that serotonin, but not dopamine, receptor mRNA expression significantly decreased in the ACC of the nicotine exposed compared to the control rats. Furthermore, there was a positive correlation between learning rate and serotonin receptor mRNA expression in the ACC. Therefore, all present results suggest that impairments in uncertainty modulation in the ACC disrupt reinforcement learning processes in chronic nicotine users and contribute to maladaptive decision-making. These findings support interventions for pathological decision-making in drug addiction that strongly focus on the serotonin system in ACC. CI - Copyright (c) 2017. Published by Elsevier Inc. FAU - Wei, Zhengde AU - Wei Z AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. FAU - Han, Long AU - Han L AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. FAU - Zhong, Xiuying AU - Zhong X AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China. FAU - Liu, Ying AU - Liu Y AD - Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230001, China. FAU - Zha, Rujing AU - Zha R AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. FAU - Wang, Ying AU - Wang Y AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. FAU - Yang, Li-Zhuang AU - Yang LZ AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. FAU - Bu, Junjie AU - Bu J AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. FAU - Song, Hongwen AU - Song H AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. FAU - Wang, Wenjuan AU - Wang W AD - School of Science, Anhui Agricultural University, Hefei, Anhui, 230036, China; School of Information Science and Technology, University of Science and Technology of China, Hefei, Anhui, 230026, China. FAU - Zhou, Yifeng AU - Zhou Y AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. FAU - Gao, Ping AU - Gao P AD - The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China. FAU - Zhang, Xiaochu AU - Zhang X AD - Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China; School of Humanities & Social Science, University of Science & Technology of China, Hefei, Anhui 230026, China; Centers for Biomedical Engineering, University of Science & Technology of China, Hefei, Anhui 230027, China; Anhui Mental Health Center, Hefei, Anhui, 230022, China. Electronic address: zxcustc@ustc.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171206 PL - United States TA - Neuroimage JT - NeuroImage JID - 9215515 RN - 0 (Receptors, Serotonin) RN - 6M3C89ZY6R (Nicotine) SB - IM MH - Animals MH - Behavior, Animal/drug effects MH - Connectome/*methods MH - Decision Making/drug effects/*physiology MH - Executive Function/drug effects/*physiology MH - Gyrus Cinguli/diagnostic imaging/drug effects/metabolism/*physiology MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Nicotine/administration & dosage/*adverse effects MH - Prefrontal Cortex/diagnostic imaging/drug effects/metabolism/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Serotonin/*drug effects MH - *Reinforcement, Psychology MH - Reward MH - Smokers MH - *Uncertainty OTO - NOTNLM OT - Addiction OT - Maladaptive decision-making OT - Reward prediction errors OT - Serotonin EDAT- 2017/12/10 06:00 MHDA- 2018/12/12 06:00 CRDT- 2017/12/10 06:00 PHST- 2017/05/10 00:00 [received] PHST- 2017/11/04 00:00 [revised] PHST- 2017/11/21 00:00 [accepted] PHST- 2017/12/10 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2017/12/10 06:00 [entrez] AID - S1053-8119(17)30993-X [pii] AID - 10.1016/j.neuroimage.2017.11.048 [doi] PST - ppublish SO - Neuroimage. 2018 Apr 1;169:323-333. doi: 10.1016/j.neuroimage.2017.11.048. Epub 2017 Dec 6.