PMID- 29882089 OWN - NLM STAT- MEDLINE DCOM- 20201106 LR - 20201106 IS - 1433-8491 (Electronic) IS - 0940-1334 (Print) IS - 0940-1334 (Linking) VI - 270 IP - 2 DP - 2020 Mar TI - Brain-derived neurotrophic factor-TrkB signaling in the medial prefrontal cortex plays a role in the anhedonia-like phenotype after spared nerve injury. PG - 195-205 LID - 10.1007/s00406-018-0909-z [doi] AB - Although depressive symptoms including anhedonia (i.e., loss of pleasure) frequently accompany pain, little is known about the risk factors contributing to individual differences in pain-induced anhedonia. In this study, we examined if signaling of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-receptor-kinase B (TrkB) contribute to individual differences in the development of neuropathic pain-induced anhedonia. Rats were randomly subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups based on the results of a sucrose preference test. Rats with anhedonia-like phenotype displayed lower tissue levels of BDNF in the medial prefrontal cortex (mPFC) compared with rats without anhedonia-like phenotype and sham-operated rats. In contrast, tissue levels of BDNF in the nucleus accumbens (NAc) of rats with an anhedonia-like phenotype were higher compared with those of rats without anhedonia-like phenotype and sham-operated rats. Furthermore, tissue levels of BDNF in the hippocampus, L2-5 spinal cord, muscle, and liver from both rats with or without anhedonia-like phenotype were lower compared with those of sham-operated rats. A single injection of 7,8-dihydroxyflavone (10 mg/kg; TrkB agonist), but not ANA-12 (0.5 mg/kg; TrkB antagonist), ameliorated reduced sucrose preference and reduced BDNF-TrkB signaling in the mPFC in the rats with anhedonia-like phenotype. These findings suggest that reduced BDNF-TrkB signaling in the mPFC might contribute to neuropathic pain-induced anhedonia, and that TrkB agonists could be potential therapeutic drugs for pain-induced anhedonia. FAU - Fang, Xi AU - Fang X AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Yang, Chun AU - Yang C AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Li, Shan AU - Li S AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Zhan, Gaofeng AU - Zhan G AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Zhang, Jie AU - Zhang J AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Huang, Niannian AU - Huang N AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Du, Xiangxi AU - Du X AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Xu, Hui AU - Xu H AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Hashimoto, Kenji AU - Hashimoto K AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan. hashimoto@faculty.chiba-u.jp. FAU - Luo, Ailin AU - Luo A AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. alluo@tjh.tjmu.edu.cn. LA - eng GR - 81771159/National Natural Science Foundation of China/ GR - 81500931/National Natural Science Foundation of China/ GR - 81703482/National Natural Science Foundation of China/ GR - JP17dm0107119/Japan Agency for Medical Research and Development/ PT - Journal Article DEP - 20180607 PL - Germany TA - Eur Arch Psychiatry Clin Neurosci JT - European archives of psychiatry and clinical neuroscience JID - 9103030 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 57-50-1 (Sucrose) RN - EC 2.7.10.1 (Ntrk2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Anhedonia/drug effects/*physiology MH - Animals MH - Behavior, Animal/drug effects/*physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Disease Models, Animal MH - Male MH - Neuralgia/etiology/*metabolism/*physiopathology MH - Nucleus Accumbens/metabolism MH - Peripheral Nerve Injuries/complications/physiopathology MH - Phenotype MH - Prefrontal Cortex/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/agonists/antagonists & inhibitors/*metabolism MH - Signal Transduction/drug effects/*physiology MH - Sucrose PMC - PMC7036057 OTO - NOTNLM OT - Anhedonia OT - BDNF OT - Individual differences OT - Neuropathic pain OT - TrkB COIS- Dr. Chun Yang received the research support from B. Braun Medical Inc. Other authors declared no conflict of interest. EDAT- 2018/06/09 06:00 MHDA- 2020/11/11 06:00 PMCR- 2018/06/07 CRDT- 2018/06/09 06:00 PHST- 2018/04/11 00:00 [received] PHST- 2018/05/31 00:00 [accepted] PHST- 2018/06/09 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2018/06/09 06:00 [entrez] PHST- 2018/06/07 00:00 [pmc-release] AID - 10.1007/s00406-018-0909-z [pii] AID - 909 [pii] AID - 10.1007/s00406-018-0909-z [doi] PST - ppublish SO - Eur Arch Psychiatry Clin Neurosci. 2020 Mar;270(2):195-205. doi: 10.1007/s00406-018-0909-z. Epub 2018 Jun 7.