{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:03Z","timestamp":1760146563336,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Audiology Research"],"abstract":"<jats:p>Background\/Objectives: Tinnitus is a debilitating auditory disorder commonly described as a ringing in the ears in the absence of an external sound source. Sound trauma is considered a primary cause. Neuronal hyperactivity is one potential mechanism for the genesis of tinnitus and has been identified in the cochlear nucleus (CN) and the auditory cortex (AC), where there may be an imbalance of excitatory and inhibitory neurotransmissions. However, no study has directly correlated tinnitus with the extracellular levels of amino acids in the CN and the AC using microdialysis, which reflects the functions of these neurochemicals. In the present study, rats were exposed to acoustic trauma and then subjected to behavioural confirmation of tinnitus after one month, followed by microdialysis. Methods: Rats were divided into sham (aged, n = 6; young, n = 6); tinnitus-positive (aged, n = 7; young, n = 7); and tinnitus-negative (aged, n = 3; young, n = 3) groups. In vivo microdialysis was utilized to collect samples from the CN and the AC, simultaneously, in the same rat. Extracellular levels of amino acids were quantified using high-performance liquid chromatography (HPLC) coupled with an electrochemical detector (ECD). The effects of sound stimulation and age on neurochemical changes associated with tinnitus were also examined. Results: There were no significant differences in either the basal levels or the sound stimulation-evoked changes of any of the amino acids examined in the CN and the AC between the sham and tinnitus animals. However, the basal levels of serine and threonine exhibited age-related alterations in the AC, and significant differences in threonine and glycine levels were observed in the responses to 4 kHz and 16 kHz stimuli in the CN. Conclusions: These results demonstrate the lack of a direct link between extracellular levels of amino acids in the CN and the AC and tinnitus perception in a rat model of tinnitus.<\/jats:p>","DOI":"10.3390\/audiolres14060083","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:37:35Z","timestamp":1732099055000},"page":"1000-1013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lack of Amino Acid Alterations Within the Cochlear Nucleus and the Auditory Cortex in Acoustic Trauma-Induced Tinnitus Rats Using In Vivo Microdialysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Shanshan","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Biomedical and Molecular Sciences, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"The Eisdell Moore Centre for Research on Hearing and Balance Disorders, University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5790-8131","authenticated-orcid":false,"given":"Huey Tieng","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Biomedical and Molecular Sciences, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"The Eisdell Moore Centre for Research on Hearing and Balance Disorders, University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-7118","authenticated-orcid":false,"given":"Paul F.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Biomedical and Molecular Sciences, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"The Eisdell Moore Centre for Research on Hearing and Balance Disorders, University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Biomedical and Molecular Sciences, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"The Eisdell Moore Centre for Research on Hearing and Balance Disorders, University of Auckland, Auckland 1010, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3109\/14992027.2010.551220","article-title":"Tinnitus and its risk factors in the Beaver Dam offspring study","volume":"50","author":"Nondahl","year":"2011","journal-title":"Int. J. Audiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/03655230600895309","article-title":"Summary of evidence pointing to a role of the dorsal cochlear nucleus in the etiology of tinnitus","volume":"126","author":"Kaltenbach","year":"2006","journal-title":"Acta Otolaryngol. Suppl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3109\/00016489409126031","article-title":"Effects of electrical brainstem stimulation on tinnitus","volume":"114","author":"Soussi","year":"1994","journal-title":"Acta Otolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1523\/JNEUROSCI.22-06-02383.2002","article-title":"Elevated fusiform cell activity in the dorsal cochlear nucleus of chinchillas with psychophysical evidence of tinnitus","volume":"22","author":"Brozoski","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0304-3940(98)00482-0","article-title":"Increases in spontaneous activity in the dorsal cochlear nucleus of the rat following exposure to high-intensity sound","volume":"250","author":"Zhang","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0378-5955(99)00197-5","article-title":"Hyperactivity in the dorsal cochlear nucleus after intense sound exposure and its resemblance to tone-evoked activity: A physiological model for tinnitus","volume":"140","author":"Kaltenbach","year":"2000","journal-title":"Hear. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.heares.2005.02.013","article-title":"Tinnitus as a plastic phenomenon and its possible neural underpinnings in the dorsal cochlear nucleus","volume":"206","author":"Kaltenbach","year":"2005","journal-title":"Hear. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.heares.2004.12.013","article-title":"The effect of dorsal cochlear nucleus ablation on tinnitus in rats","volume":"206","author":"Brozoski","year":"2005","journal-title":"Hear. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10162-011-0290-3","article-title":"Bilateral dorsal cochlear nucleus lesions prevent acoustic-trauma induced tinnitus in an animal model","volume":"13","author":"Brozoski","year":"2012","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1152\/jn.1995.73.1.227","article-title":"Synchrony between single-unit activity and local field potentials in relation to periodicity coding in primary auditory cortex","volume":"73","author":"Eggermont","year":"1995","journal-title":"J. Neurophysiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.neuroscience.2009.12.063","article-title":"Neural changes in the auditory cortex of awake guinea pigs after two tinnitus inducers: Salicylate and acoustic trauma","volume":"166","author":"Norena","year":"2009","journal-title":"Neuroscience"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature09656","article-title":"Reversing pathological neural activity using targeted plasticity","volume":"470","author":"Engineer","year":"2011","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0378-5955(03)00074-1","article-title":"Changes in spontaneous firing rate and neural synchrony in cat primary auditory cortex after localized tone-induced hearing loss","volume":"180","author":"Seki","year":"2003","journal-title":"Hear. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10162-010-0246-z","article-title":"Auditory cortex electrical stimulation suppresses tinnitus in rats","volume":"12","author":"Zhang","year":"2011","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1227\/01.NEU.0000103420.53487.79","article-title":"Functional anatomy of the human cochlear nerve and its role in microvascular decompressions for tinnitus","volume":"54","author":"Ryu","year":"2004","journal-title":"Neurosurgery"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14974","DOI":"10.1073\/pnas.1107998108","article-title":"Homeostatic plasticity drives tinnitus perception in an animal model","volume":"108","author":"Yang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","unstructured":"Van Dongen, A.M. (2009). Biology of the NMDA Receptor Frontiers in Neuroscience, Frontiers."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/jnr.20011","article-title":"Noise trauma alters D-[3H]aspartate release and AMPA binding in chinchilla cochlear nucleus","volume":"75","author":"Muly","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1002\/jnr.23095","article-title":"Amino acid concentrations in the hamster central auditory system and long-term effects of intense tone exposure","volume":"90","author":"Godfrey","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.neuroscience.2007.12.031","article-title":"Effects of cochlear ablation on amino acid concentrations in the chinchilla posteroventral cochlear nucleus, as compared to rat","volume":"154","author":"Godfrey","year":"2008","journal-title":"Neuroscience"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108948","DOI":"10.1016\/j.heares.2024.108948","article-title":"Time-dependent effects of acoustic trauma and tinnitus on extracellular levels of amino acids in the inferior colliculus of rats","volume":"443","author":"Tan","year":"2024","journal-title":"Hear. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuroscience.2011.04.052","article-title":"The effects of acoustic trauma that can cause tinnitus on spatial performance in rats","volume":"186","author":"Zheng","year":"2011","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.neuropharm.2011.09.027","article-title":"A dose-response analysis of the effects of L-baclofen on chronic tinnitus caused by acoustic trauma in rats","volume":"62","author":"Zheng","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_24","unstructured":"Paxinos, G., and Watson, C. (2013). The Rat Brain in Stereotaxic Coordinates, Elsevier. [7th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1002\/sim.4293","article-title":"Avoiding bias in mixed model inference for fixed effects","volume":"30","author":"Gurka","year":"2011","journal-title":"Stat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.neulet.2014.11.047","article-title":"Glutamic acid decarboxylase levels in the cochlear nucleus of rats with acoustic trauma-induced chronic tinnitus","volume":"586","author":"Zheng","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1121\/1.387996","article-title":"Measurement of basilar membrane motion in the guinea pig using the Mossbauer technique","volume":"72","author":"Sellick","year":"1982","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13452","DOI":"10.1523\/JNEUROSCI.2156-11.2011","article-title":"Tinnitus with a normal audiogram: Physiological evidence for hidden hearing loss and computational model","volume":"31","author":"Schaette","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/bs.pbr.2020.01.006","article-title":"Separate auditory pathways for the induction and maintenance of tinnitus and hyperacusis?","volume":"260","author":"Eggermont","year":"2021","journal-title":"Prog. Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.brainres.2012.03.044","article-title":"Understanding tinnitus: The dorsal cochlear nucleus, organization and plasticity","volume":"1485","author":"Baizer","year":"2012","journal-title":"Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neuron.2019.05.008","article-title":"Mechanisms of noise-induced tinnitus: Insights from cellular studies","volume":"103","author":"Shore","year":"2019","journal-title":"Neuron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14822","DOI":"10.1523\/JNEUROSCI.2695-15.2015","article-title":"Human auditory cortex neurochemistry reflects the presence and severity of tinnitus","volume":"35","author":"Sedley","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00441-013-1709-4","article-title":"Brain microdialysis and its applications in experimental neurochemistry","volume":"354","author":"Anderzhanova","year":"2013","journal-title":"Cell Tissue Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2005.01.017","article-title":"Microdialysis\u2013theoretical background and recent implementation in applied life-sciences","volume":"25","author":"Plock","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0378-5955(02)00708-6","article-title":"Effects of salicylate on serotoninergic activities in rat inferior colliculus and auditory cortex","volume":"175","author":"Liu","year":"2003","journal-title":"Hear. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/BF00964918","article-title":"Changes with aging in the levels of amino acids in rat CNS structural elements.3I. Glutamate and related amino acids","volume":"14","author":"Lajtha","year":"1989","journal-title":"Neurochem. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.heares.2017.05.002","article-title":"Amino acid and acetylcholine chemistry in the central auditory system of young, middle-aged and old rats","volume":"350","author":"Godfrey","year":"2017","journal-title":"Hear. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1111\/j.1460-9568.2010.07183.x","article-title":"Acoustic trauma evokes hyperactivity and changes in gene expression in guinea-pig auditory brainstem","volume":"31","author":"Dong","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Barker, M., Solinski, H.J., Hashimoto, H., Tagoe, T., Pilati, N., and Hamann, M. (2012). Acoustic overexposure increases the expression of VGLUT-2 mediated projections from the lateral vestibular nucleus to the dorsal cochlear nucleus. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035955"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Browne, C.J., Morley, J.W., and Parsons, C.H. (2012). Tracking the expression of excitatory and inhibitory neurotransmission-related proteins and neuroplasticity markers after noise induced hearing loss. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033272"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.brainres.2010.04.067","article-title":"Tonotopic changes in GABA receptor expression in guinea pig inferior colliculus after partial unilateral hearing loss","volume":"1342","author":"Dong","year":"2010","journal-title":"Brain Res."}],"container-title":["Audiology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4349\/14\/6\/83\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:04Z","timestamp":1760114044000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4349\/14\/6\/83"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,17]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["audiolres14060083"],"URL":"https:\/\/doi.org\/10.3390\/audiolres14060083","relation":{},"ISSN":["2039-4349"],"issn-type":[{"type":"electronic","value":"2039-4349"}],"subject":[],"published":{"date-parts":[[2024,11,17]]}}}