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Preliminary study on the mechanism underlying the interaction of balance dysfunction and anxiety disorder

Zhai, Fenga,*; Shi, Fangb,*; Wang, Jingb,*; Dai, Chun-Fub,c; Fan, Chunsund

doi: 10.1097/WNR.0000000000000977

This study aims to explore the anxiety-related behavioral changes and the concentration alterations of monoamine neurotransmitters in balance/anxiety-related nuclei of intratympanic gentamicin (GT)-induced balance disorder models. GT was administrated intratympanically in the adult male Sprague-Dawley rats to establish the vestibular impaired animal model. Rotarod was applied to test the vestibular function, and elevated plus maze and open field test were harnessed to evaluate the anxiety level. Monoamines and their metabolites were assayed by high-performance liquid chromatography. Rotarod test revealed that 6 days after GT administration, the average latency decreased significantly compared with the control group. Three days after GT administration, the travel distance and the central zone time obtained from open field and the duration of open arm stay and the times of open arm entries from elevated plus maze were apparently lower than those of the control group, whereas no significant differences were noted between 2-week group and the control group. Three days after GT administration, the concentration of norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) within medial vestibular nucleus (MVN); the concentration of NE, serotonin (5-HT), and 5-HIAA within locus coeruleus (LC); and the concentration of NE, 5-HT, 5-HIAA, and 3,4-dihydroxyphenylacetic acid within dorsal raphe nucleus (DRN) increased significantly compared with the control group. Two weeks after the administration, the concentrations of part of the neurotransmitters were lower than those of the 3-day group, indicating the rapid activation and slow deactivation of MVN-LC and MVN-DRN pathways. Vestibular impairment could lead to elevated anxiety level. The elevated anxiety levels might be attributed to increased monoamine concentrations within MVN, LC, and DRN.

aDepartment of Otolaryngology, School of Medicine, Shanghai Children’s Medical Center, Affiliated to Shanghai Jiaotong University

bDepartment of Otology and Skull Base Surgery, Eye and Ear Nose and Throat Hospital

cHearing Research Key Lab of Health Ministry of China, Fudan University, Shanghai

dDepartment of Etiology, Qidong People’s Hospital, Qidong, China

* Feng Zhai, Fang Shi and Jing Wang contributed equally to the writing of this article.

Correspondence to Chun-Fu Dai, MD, PhD, Department of Otology and Skull Base Surgery, Eye and Ear Nose Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China Tel: +86 021 6437 7134; fax: +86 021 6437 7151; e-mail:

Received November 23, 2017

Accepted December 11, 2017

© 2019 Wolters Kluwer Health | Lippincott Williams & Wilkins