title: Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS.
abstract: Tinnitus is associated with neural hyperactivity in the central nervous system (CNS). Salicylate is a well-known ototoxic drug, and we induced tinnitus in rats using a model of long-term salicylate administration. The gap pre-pulse inhibition of acoustic startle test was used to infer tinnitus perception, and only rats in the chronic salicylate-treatment (14 days) group showed evidence of experiencing tinnitus. After small animal positron emission tomography scans were performed, we found that the metabolic activity of the inferior colliculus (IC), the auditory cortex (AC), and the hippocampus (HP) were significantly higher in the chronic treatment group compared with saline group (treated for 14 days), which was further supported by ultrastructural changes at the synapses. The alterations all returned to baseline 14 days after the cessation of salicylate-treatment (wash-out group), indicating that these changes were reversible. These findings indicate that long-term salicylate administration induces tinnitus, enhanced neural activity and synaptic ultrastructural changes in the IC, AC, and HP of rats due to neuroplasticity. Thus, an increased metabolic rate and synaptic transmission in specific areas of the CNS may contribute to the development of tinnitus.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.|Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province China.
authors.forename: Shousen
authors.initials: S
authors.lastname: Hu
authors.affiliation: PET Center, Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai China.
authors.forename: Chuantao
authors.initials: C
authors.lastname: Zuo
authors.affiliation: PET Center, Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai China.
authors.forename: Fangyang
authors.initials: F
authors.lastname: Jiao
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.
authors.forename: Jingrong
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.|Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.|Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.|Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.|Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.|Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai China.|Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001303:Auditory Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000648:ultrastructure; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000648:ultrastructure; D007245:Inferior Colliculi / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000648:ultrastructure; D049268:Positron-Emission Tomography; D012459:Salicylates / Q000008:administration & dosage / Q000009:adverse effects*; D013569:Synapses / Q000187:drug effects* / Q000648:ultrastructure; D014012:Tinnitus / Q000139:chemically induced*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates